takaoka.katsuyoshi/published_papers/51774377 Takafumi Sakai Masahiro Kawakita# Arashi Seki# Katsuyoshi Takaoka# Misaki Kurata Junpei Torikai Sohshiroh Atsumi Kanji Yawata Kentaro Noi Yosuke Fukutani Keiichi Noguchi Hirofumi Kiyokawa Mitsuru Morimoto Eri Takeuchi Katsura Minegishi Yoshitsugu Aoki Shoko Fujimura Takayuki Nishizaka Takanari Inoue Kentaro Nagaoka Hiroshi Tsugawa Hisayoshi Hayashi Hiroshi Ishiguro Takuma Kozono Ikuroh Ohsawa Yasunori Fujita Hiroaki Matsunami Hiroshi Hamada Kyosuke Shinohara Tppp3 determines basal body positioning and identity of respiratory cilia via microtubule assembly and sphingolipid homeostasis Proceedings of the National Academy of Sciences null null 20251209 10.1073/pnas.2503931122 takaoka.katsuyoshi/published_papers/51194025 Megumi Murata Akihito Harada Haruka Hirose Hinako Maeda Teppei Shimamura Yasuyuki Ohkawa Tatsuya Takemoto Katsuyoshi Takaoka p53-mediated regulation of epiblast cell numbers predicts reactivation during mouse embryonic diapause Cell Reports null null 20251000 10.1016/j.celrep.2025.116298 takaoka.katsuyoshi/published_papers/50720635 Hinako MAEDA Katsuyoshi TAKAOKA Percentage of cell cycle phases in diapause embryo cells across developmental stages p53-mediated regulation of epiblast cell numbers predicts reactivation during mouse embryonic diapauseMegumi Murata, Akihito Harada, Haruka Hirose, Hinako Maeda, Teppei Shimamura, Yasuyuki Ohkawa, Tatsuya Takemoto, and Katsuyoshi Takaoka* Figshare null null 20250911 10.6084/m9.figshare.29653463 takaoka.katsuyoshi/published_papers/49353311 Ritsuko Nakai Takafumi Yokota Masahiro Tokunaga Mikiro Takaishi Tomomasa Yokomizo Takao Sudo Henyun Shi Yoshiaki Yasumizu Daisuke Okuzaki Chikara Kokubu Sachiyo Tanaka Katsuyoshi Takaoka Ayako Yamanishi Junko Yoshida Hitomi Watanabe Gen Kondoh Kyoji Horie Naoki Hosen Shigetoshi Sano Junji Takeda Author Correction: A newly identified gene Ahed plays essential roles in murine haematopoiesis. Nature communications 15 1 9134 9134 20241023 10.1038/s41467-024-53499-5 39443487 takaoka.katsuyoshi/published_papers/48282436 実験医学完全休養か?部分的休養か?哺乳類胚の多様な休み方実験医学 null null 20240900 takaoka.katsuyoshi/published_papers/46906677 Katarina Harasimov Rebecca L. Gorry Luisa M. Welp Sarah Mae Penir Yehor Horokhovskyi Shiya Cheng Katsuyoshi Takaoka Alexandra Stützer Ann-Sophie Frombach Ana Lisa Taylor Tavares Monika Raabe Sara Haag Debojit Saha Katharina Grewe Vera Schipper Silvio O. Rizzoli Henning Urlaub Juliane Liepe Melina Schuh The maintenance of oocytes in the mammalian ovary involves extreme protein longevity Women are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman's reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline. AbstractWomen are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman's reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline. Springer Science and Business Media LLC Nature Cell Biology 1476-4679 26 7 1124 1138 20240700 10.1038/s41556-024-01442-7 38902423 1872836541392469632 takaoka.katsuyoshi/published_papers/46906676 Ritsuko Nakai Ritsuko Nakai:Takafumi Yokota:Masahiro Tokunaga Takafumi Yokota Mikiro Takaishi Masahiro Tokunaga Takao Sudo Mikiro Takaishi Henyun Shi Tomomasa Yokomizo Yoshiaki Yasumizu Takao Sudo Daisuke Okuzaki Henyun Shi Chikara Kokubu Yoshiaki Yasumizu Sachiyo Tanaka Daisuke Okuzaki Katsuyoshi Takaoka Chikara Kokubu Ayako Yamanishi Sachiyo Tanaka Junko Yoshida Katsuyoshi Takaoka Hitomi Watanabe Ayako Yamanishi Gen Kondoh Junko Yoshida Kyoji Horie Hitomi Watanabe Naoki Hosen Gen Kondoh Shigetoshi Sano Kyoji Horie Junji Takeda Naoki Hosen Shigetoshi Sano Junji Takeda A newly identified gene Ahed plays essential roles in murine haematopoiesis. A newly identified gene Ahed plays essential roles in haematopoiesis through RNA splicing The development of haematopoiesis involves the coordinated action of numerous genes, some of which are implicated in haematological malignancies. However, the biological function of many genes remains elusive and unknown functional genes are likely to remain to be uncovered. Here, we report a previously uncharacterised gene in haematopoiesis, identified by screening mutant embryonic stem cells. The gene, 'attenuated haematopoietic development (Ahed)', encodes a nuclear protein. Conditional knockout (cKO) of Ahed results in anaemia from embryonic day 14.5 onward, leading to prenatal demise. Transplantation experiments demonstrate the incapacity of Ahed-deficient haematopoietic cells to reconstitute haematopoiesis in vivo. Employing a tamoxifen-inducible cKO model, we further reveal that Ahed deletion impairs the intrinsic capacity of haematopoietic cells in adult mice. Ahed deletion affects various pathways, and published databases present cancer patients with somatic mutations in Ahed. Collectively, our findings underscore the fundamental roles of Ahed in lifelong haematopoiesis, implicating its association with malignancies. <title>Abstract</title> The development of haematopoiesis is regulated by coordinated actions of multiple genes. Mutations in some genes are intimately involved in the occurrence of haematological cancers. Here, we report a previously undefined functional gene in haematopoiesis, which we isolated by screening mutant embryonic stem cells. The gene, named ``<italic>attenuated haematopoietic development</italic>'' (<italic>Ahed</italic>), encoded an uncharacterized nuclear protein. We found that <italic>Ahed</italic> conditional knock out (cKO) foetuses became anaemic after E14.5 and died before birth. Transplantation experiments revealed that <italic>Ahed</italic>-deficient lineage-Sca-1+c-KitHi cells were unable to reconstitute haematopoiesis <italic>in vivo</italic>, suggesting that <italic>Ahed</italic> is indispensable for functional haematopoietic stem/progenitor cells. Multiple RNA sequencing analyses of <italic>Ahed</italic>-cKO cells revealed that this protein governs various critical pathways by regulating alternative splicing of RNAs. Published databases of cancer-related mutations present blood cancer patients with somatic mutations in the <italic>Ahed</italic> gene. Thus, <italic>Ahed</italic> plays a fundamental role in haematopoiesis through RNA splicing, whose mutations relates to malignancies. Research Square Platform LLC Nature communications Nature Communications 2041-1723 15 1 5090 5090 20240625 10.1038/s41467-024-49252-7 38918373 1873116917450565120 takaoka.katsuyoshi/published_papers/46310070 Yumiko Hayashi Masakazu Hashimoto Katsuyoshi Takaoka Tatsuya Takemoto Nobuyuki Takakura Hiroyasu Kidoya Tumor endothelial cell-derived Sfrp1 supports the maintenance of cancer stem cells via Wnt signaling. Tumor endothelial cell-derived Sfrp1 supports the maintenance of cancer stem cells via Wnt signaling Cancer stem cells (CSCs), which are critical targets for cancer therapy as they are involved in drug resistance to anticancer drugs, and metastasis, are maintained by angiocrine factors produced by particular niches that form within tumor tissue. Secreted frizzled-related protein 1 (Sfrp1) is an extracellular protein that modulates Wnt signaling. However, the cells that produce Sfrp1 in the tumor environment and its function remain unclear. We aimed to elucidate angiocrine factors related to CSC maintenance, focusing on Sfrp1. Although Sfrp1 is a Wnt pathway-related factor, its impact on tumor tissues remains unknown. We investigated the localization of Sfrp1 in tumors and found that it is expressed in some tumor vessels. Analysis of mice lacking Sfrp1 showed that tumor growth was suppressed in Sfrp1-deficient tumor tissues. Flow cytometry analysis indicated that CSCs were maintained in the early tumor growth phase in the Sfrp1 knockout (KO) mouse model of tumor-bearing cancer. However, tumor growth was inhibited in the late tumor growth phase because of the inability to maintain CSCs. Real-time PCR results from tumors of Sfrp1 KO mice showed that the expression of Wnt signaling target genes significantly decreased in the late stage of tumor growth. This suggests that Sfrp1, an angiocrine factor produced by the tumor vascular niche, is involved in Wnt signaling-mediated mechanisms in tumor tissues. AbstractCancer stem cells (CSCs), which are critical targets for cancer therapy as they are involved in drug resistance to anticancer drugs, and metastasis, are maintained by angiocrine factors produced by particular niches that form within tumor tissue. Secreted frizzled-related protein 1 (Sfrp1) is an extracellular protein that modulates Wnt signaling. However, the cells that produce Sfrp1 in the tumor environment and its function remain unclear. We aimed to elucidate angiocrine factors related to CSC maintenance, focusing on Sfrp1. Although Sfrp1 is a Wnt pathway-related factor, its impact on tumor tissues remains unknown. We investigated the localization of Sfrp1 in tumors and found that it is expressed in some tumor vessels. Analysis of mice lacking Sfrp1 showed that tumor growth was suppressed in Sfrp1-deficient tumor tissues. Flow cytometry analysis indicated that CSCs were maintained in the early tumor growth phase in the Sfrp1 knockout (KO) mouse model of tumor-bearing cancer. However, tumor growth was inhibited in the late tumor growth phase because of the inability to maintain CSCs. Real-time PCR results from tumors of Sfrp1 KO mice showed that the expression of Wnt signaling target genes significantly decreased in the late stage of tumor growth. This suggests that Sfrp1, an angiocrine factor produced by the tumor vascular niche, is involved in Wnt signaling-mediated mechanisms in tumor tissues. Springer Science and Business Media LLC In vitro cellular & developmental biology. Animal In Vitro Cellular & Developmental Biology - Animal 1543-706X 60 10 1123 1131 20240416 10.1007/s11626-024-00899-y 38625488 1360865814726679808 takaoka.katsuyoshi/published_papers/41960648 Sylvain Hiver Sylvain, Hiver Natsumi Shimizu-Mizuno Natsumi, Shimizu-Mizuno Yayoi Ikawa Yayoi, Ikawa Eriko Kajikawa Eriko, Kajikawa Xiaorei Sai Xiaorei, Sai Hiromi Nishimura Hiromi, Nishimura Katsuyoshi Takaoka Katsuyoshi, Takaoka Osamu Nishimura Osamu, Nishimura Shigehiro Kuraku Shigehiro, Kuraku Satomi Tanaka Satoshi, Tanaka Hiroshi Hamada Hiroshi, Hamada Gse1, a component of the CoREST complex, is required for placenta development in the mouse. Gse1, a component of the CoREST complex, is required for placenta development in the mouse Gse1 is a component of the CoREST complex that acts as an H3K4 and H3K9 demethylase and regulates gene expression. Here, we examined the expression and role of Gse1 in mouse development. Gse1 is expressed in male and female germ cells and plays both maternal and zygotic roles. Thus, maternal deletion of Gse1 results in a high incidence of prenatal death, and zygotic deletion leads to embryonic lethality from embryonic day 12.5 (E12.5) and perinatal death. Gse1 is expressed in the junctional zone and the labyrinth of the developing placenta. Cultured trophoblast stem cells lacking Gse1 showed impaired in vitro cell differentiation into spongiotrophoblasts. Gse1 mutant (Gse1Δex3/Δex3) placenta begins to exhibit histological defects from E14.5, being deficient in MCT4+ syncytiotrophoblast II. The number of various cell types was largely maintained in the mutant placenta at E10.5, but several genes were upregulated in giant trophoblasts at E10.5. Placenta-specific deletion of Gse1 with Tat-Cre suggested that defects in Gse1Δex3/Δex3 embryos are due to placental function deficiency. These results suggest that Gse1 is required for placental development in mice, and in turn, is essential for embryonic development. Gse1 is a component of the CoREST complex that acts as an H3K4 and H3K9 demethylase and regulates gene expression. Here, we examined the expression and role of Gse1 in mouse development. Gse1 is expressed in male and female germ cells and plays both maternal and zygotic roles. Thus, maternal deletion of Gse1 results in a high incidence of prenatal death, and zygotic deletion leads to embryonic lethality from embryonic day 12.5 (E12.5) and perinatal death. Gse1 is expressed in the junctional zone and the labyrinth of the developing placenta. Gse1 mutant (Gse1 Elsevier BV Developmental biology Developmental Biology 0012-1606 498 97 105 20230403 10.1016/j.ydbio.2023.03.009 37019373 1871428068115013248 takaoka.katsuyoshi/published_papers/36785040 Xiaorei Sai Yayoi Ikawa Hiromi Nishimura Katsutoshi Mizuno Eriko Kajikawa Takanobu A Katoh Takanobu A. Katoh Toshiya Kimura Hidetaka Shiratori Katsuyoshi Takaoka Hiroshi Hamada Katsura Minegishi Planar cell polarity-dependent asymmetric organization of microtubules for polarized positioning of the basal body in node cells. Planar cell polarity-dependent asymmetric organization of microtubules for polarized positioning of the basal body in node cells For left-right symmetry breaking in the mouse embryo, the basal body must become positioned at the posterior side of node cells, but its precise mechanism has remained unknown. We here examined the role of microtubules (MTs) and actomyosin in this basal body positioning. Exposure of mouse embryos to agents that stabilize or destabilize MTs or F-actin impaired such positioning. Active myosin II was detected at the anterior side of node cells before the posterior shift of the basal body, and this asymmetric activation was lost in Prickle and Dachsous mutant embryos. The organization of basal-body associated MTs (baMTs) was asymmetric between the anterior and posterior sides of node cells, with anterior baMTs extending horizontally and posterior baMTs extending vertically. This asymmetry became evident after polarization of the PCP core protein Vangl1 and before the posterior positioning of the basal body, and it also required the PCP core proteins Prickle and Dachsous. Our results suggest that the asymmetry in baMT organization may play a role in correct positioning of the basal body for left-right symmetry breaking. ABSTRACT For left-right symmetry breaking in the mouse embryo, the basal body must become positioned at the posterior side of node cells, but the precise mechanism for this has remained unknown. Here, we examined the role of microtubules (MTs) and actomyosin in this basal body positioning. Exposure of mouse embryos to agents that stabilize or destabilize MTs or F-actin impaired such positioning. Active myosin II was detected at the anterior side of node cells before the posterior shift of the basal body, and this asymmetric activation was lost in Prickle and dachsous mutant embryos. The organization of basal-body associated MTs (baMTs) was asymmetric between the anterior and posterior sides of node cells, with anterior baMTs extending horizontally and posterior baMTs extending vertically. This asymmetry became evident after polarization of the PCP core protein Vangl1 and before the posterior positioning of the basal body, and it also required the PCP core proteins Prickle and dachsous. Our results suggest that the asymmetry in baMT organization may play a role in correct positioning of the basal body for left-right symmetry breaking. The Company of Biologists Development (Cambridge, England) Development 1477-9129 149 9 null null 20220414 10.1242/dev.200315 35420656 1360294740583644032 takaoka.katsuyoshi/published_papers/36785048 浜崎祥生高岡勝吉* 受精と胚発生をめぐる話題哺乳類着床前胚における発生休止 Hormone Frontier in Gynecology 1340-220X 29 1 null null 20220000 takaoka.katsuyoshi/published_papers/33006463 Katsura Minegishi Benjamin Rothé Kaoru R Komatsu Kaoru R. Komatsu Hiroki Ono Yayoi Ikawa Hiromi Nishimura Takanobu A Katoh Emi Miyashita Eriko Kajikawa Katsuyoshi Takaoka Xiaorei Sai Kana Bando Emi Miyashita Hiroshi Kiyonari Katsuyoshi Takaoka Tadashi Yamamoto Kana Bando Hirohide Saito Hiroshi Kiyonari Daniel B. Constam Tadashi Yamamoto Hiroshi Hamada Hirohide Saito Daniel B Constam Hiroshi Hamada Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex. Fluid flow-induced left-right asymmetric decay ofDand5mRNA in the mouse embryo requires Bicc1-Ccr4 RNA degradation complex Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3' untranslated region (3'-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3'-UTR reporter transgene to Ca2+, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node. SUMMARYMolecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation ofDand5mRNA on the left side. We here examined how the fluid flow inducesDand5mRNA decay. We found that the 3' untranslated region (3'-UTR) ofDand5mRNA is necessary and sufficient for the left-sided decay and is responsive to the flow direction, loss of the cation channel Pkd2, and Ca2+. The 200-nucleotide proximal-most portion of the 3'-UTR, which is conserved among mammals, is essential for the asymmetric mRNA decay and binds Bicc1, an RNA binding protein specifically expressed at the node. Bicc1 preferentially recognizes GAC and GACR sequences in RNA, and these motifs are enriched in the 200-nucleotide region of theDand53'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required forDand5mRNA decay at the node. Our results thus suggest that leftward fluid flow induces binding of Bicc1 to the 3'-UTR ofDand5mRNA in crown cells on the left side of the node, and that consequent recruitment of Ccr4-Not mediates mRNA degradation. Cold Spring Harbor Laboratory Nature communications 2041-1723 12 1 4071 4071 20210701 10.1038/s41467-021-24295-2 34210974 1362825895848566016 takaoka.katsuyoshi/published_papers/36785055 高岡勝吉* 浜崎祥生竹本龍也 Embryonic diapause in mammals 哺乳類胚における発生休止 Bio Clinica 0919-8237 36 2 null null 20210000 takaoka.katsuyoshi/published_papers/31538919 Takahiro Ide Wang Kyaw Twan Hao Lu Yayoi Ikawa Lin-Xenia Lim Nicole Henninger Hiromi Nishimura Katsuyoshi Takaoka Vijay Narasimhan Xiumin Yan Hidetaka Shiratori Sudipto Roy Hiroshi Hamada CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components. CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53-/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types. Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia ofCfap53mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia ofCfap53-/-mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types. Public Library of Science (PLoS) PLoS genetics PLOS Genetics 1553-7404 16 12 e1009232 null 20201200 10.1371/journal.pgen.1009232 33347437 1360009142744151424 takaoka.katsuyoshi/published_papers/30783833 Gerard W Dougherty Gerard W. Dougherty Katsutoshi Mizuno Tabea Nöthe-Menchen Yayoi Ikawa Karsten Boldt Asaf Ta-Shma Isabella Aprea Katsura Minegishi Yuan-Ping Pang Petra Pennekamp Niki T Loges Niki T. Loges Johanna Raidt Rim Hjeij Julia Wallmeier Huda Mussaffi Zeev Perles Orly Elpeleg Franziska Rabert Hidetaka Shiratori Stef J Letteboer Stef J. Letteboer Nicola Horn Samuel Young Timo Strünker Friederike Stumme Claudius Werner Heike Olbrich Katsuyoshi Takaoka Takahiro Ide Wang Kyaw Twan Luisa Biebach Jörg Große-Onnebrink Judith A Klinkenbusch Judith A. Klinkenbusch Kavita Praveen Diana C Bracht Diana C. Bracht Inga M Höben Inga M. Höben Katrin Junger Jana Gützlaff Sandra Cindrić Micha Aviram Thomas Kaiser Yasin Memari Petras P Dzeja Petras P. Dzeja Bernd Dworniczak Marius Ueffing Ronald Roepman Kerstin Bartscherer Nicholas Katsanis Erica E Davis Erica E. Davis Israel Amirav Hiroshi Hamada Heymut Omran CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module. AbstractAxonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module. Springer Science and Business Media LLC Nature communications Nature Communications 2041-1723 11 1 5520 5520 20201102 10.1038/s41467-020-19113-0 33139725 1360009142741750144 takaoka.katsuyoshi/published_papers/51058379 Katsutoshi Mizuno Kei Shiozawa Takanobu A Katoh Katsura Minegishi Takahiro Ide Yayoi Ikawa Hiromi Nishimura Katsuyoshi Takaoka Takeshi Itabashi Atsuko H Iwane Junichi Nakai Hidetaka Shiratori Hiroshi Hamada Role of Ca2+ transients at the node of the mouse embryo in breaking of left-right symmetry. Immotile cilia sense extracellular signals such as fluid flow, but whether Ca2+ plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca2+ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca2+ transients were detected in the crown cells at the node. These Ca2+ transients showed L-R asymmetry, which was lost in the absence of fluid flow or the PKD2 channel. Further characterization allowed classification of the Ca2+ transients into two types: cilium-derived, L-R-asymmetric transients (type 1) and cilium-independent transients without an L-R bias (type 2). Type 1 intraciliary transients occurred preferentially at the left posterior region of the node, where L-R symmetry breaking takes place. Suppression of intraciliary Ca2+ transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca2+ transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo. Science advances 6 30 eaba1195 null 20200700 10.1126/sciadv.aba1195 32743070 takaoka.katsuyoshi/published_papers/27730480 Nobuyuki Kawamura Katsuyoshi Takaoka Hiroshi Hamada Anna-Katerina Hadjantonakis Ge-Hong Sun-Wada Yoh Wada Rab7-Mediated Endocytosis Establishes Patterning of Wnt Activity through Inactivation of Dkk Antagonism. Endocytosis has been proposed to modulate cell signaling activities. However, the role of endocytosis in embryogenesis, which requires coordination of multiple signaling inputs, has remained less understood. We previously showed that mouse embryos lacking a small guanosine triphosphate (GTP)-binding protein Rab7 implicated in endocytic flow are defective in gastrulation. Here, we investigate how subcellular defects associated with Rab7 deficiency are related to the observed developmental defects. Rab7-deficient embryos fail to organize mesodermal tissues due to defects in Wnt-β-catenin signaling. Visceral endoderm (VE)-specific ablation of Rab7 results in patterning defects similar to systemic Rab7 deletion. Rab7 mutants accumulate the Wnt antagonist Dkk1 in the extracellular space and in intracellular compartments throughout the VE epithelium. These data indicate that Rab7-dependent endocytosis regulates the concentration and availability of extracellular Dkk1, thereby relieving the epiblast of antagonism. This intercellular mechanism therefore organizes distinct spatiotemporal patterns of canonical Wnt activity during the peri-gastrulation stages of embryonic development. Cell reports 2211-1247 31 10 107733 107733 20200609 10.1016/j.celrep.2020.107733 32521258 1050304183896540672 takaoka.katsuyoshi/published_papers/24544521 高岡勝吉* 木戸屋浩康大澤毅研究者の最新動向哺乳類胚の休眠ダイナミクス (株)北隆館 Precision Medicine 2434-3625 2 14 1376 1379 20191200 takaoka.katsuyoshi/published_papers/24544463 Lynda Lamri Wang Kyaw Twan Takanobu A Katoh Takanobu A. Katoh Yanick Botilde Katsuyoshi Takaoka Yayoi Ikawa Hiromi Nishimura Akemi Fukumoto Katsura Minegishi Katsutoshi Mizuno Hiroshi Hamada Ciliogenesis-coupled accumulation of IFT-B proteins in a novel cytoplasmic compartment. Ciliogenesis‐coupled accumulation of IFT‐B proteins in a novel cytoplasmic compartment Cluap1/IFT38 is a ciliary protein that belongs to the IFT-B complex and is required for ciliogenesis. In this study, we have examined the behaviors of Cluap1 protein in nonciliated and ciliated cells. In proliferating cells, Cluap1 is located at the distal appendage of the mother centriole. When cells are induced to form cilia, Cluap1 is found in a novel noncentriolar compartment, the cytoplasmic IFT spot, which mainly exists once in a cell. Other IFT-B proteins such as IFT46 and IFT88 are colocalized in this spot. The cytoplasmic IFT spot is present in mouse embryonic fibroblasts (MEFs) but is absent in ciliogenesis-defective MEFs lacking Cluap1, Kif3a or Odf2. The cytoplasmic IFT spot is also found in mouse embryos but is absent in the Cluap1 mutant embryo. When MEFs are induced to form cilia, the cytoplasmic IFT spot appears at an early step of ciliogenesis but starts to disappear when ciliogenesis is mostly completed. These results suggest that IFT-B proteins such as Cluap1 accumulate in a previously undescribed cytoplasmic compartment during ciliogenesis. AbstractCluap1/IFT38 is a ciliary protein that belongs to the IFT‐B complex and is required for ciliogenesis. In this study, we have examined the behaviors of Cluap1 protein in nonciliated and ciliated cells. In proliferating cells, Cluap1 is located at the distal appendage of the mother centriole. When cells are induced to form cilia, Cluap1 is found in a novel noncentriolar compartment, the cytoplasmic IFT spot, which mainly exists once in a cell. Other IFT‐B proteins such as IFT46 and IFT88 are colocalized in this spot. The cytoplasmic IFT spot is present in mouse embryonic fibroblasts (MEFs) but is absent in ciliogenesis‐defective MEFs lacking Cluap1, Kif3a or Odf2. The cytoplasmic IFT spot is also found in mouse embryos but is absent in the Cluap1 mutant embryo. When MEFs are induced to form cilia, the cytoplasmic IFT spot appears at an early step of ciliogenesis but starts to disappear when ciliogenesis is mostly completed. These results suggest that IFT‐B proteins such as Cluap1 accumulate in a previously undescribed cytoplasmic compartment during ciliogenesis. Wiley Genes to cells : devoted to molecular & cellular mechanisms Genes to Cells 1365-2443 24 11 731 745 20191100 10.1111/gtc.12722 31554018 1360005520522134912 takaoka.katsuyoshi/published_papers/24544464 Katsuyoshi Takaoka* Katsuyoshi Takaoka Hiromi Nishimura Hiroshi Hamada Both Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos. Both Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos Anterior-posterior (A-P) polarity of mouse embryos is established by distal visceral endoderm (DVE) at embryonic day (E) 5.5. Lefty1 is expressed first at E3.5 in a subset of epiblast progenitor cells (L1epi cells) and then in a subset of primitive endoderm cells (L1dve cells) fated to become DVE. Here we studied how prospective DVE cells are selected. Lefty1 expression in L1epi and L1dve cells depends on Nodal signaling. A cell that experiences the highest level of Nodal signaling begins to express Lefty1 and becomes an L1epi cell. Deletion of Lefty1 alone or together with Lefty2 increased the number of prospective DVE cells. Ablation of L1epi or L1dve cells triggered Lefty1 expression in a subset of remaining cells. Our results suggest that selection of prospective DVE cells is both random and regulated, and that a fixed prepattern for the A-P axis does not exist before the blastocyst stage. AbstractAnterior–posterior (A–P) polarity of mouse embryos is established by distal visceral endoderm (DVE) at embryonic day (E) 5.5. Lefty1 is expressed first at E3.5 in a subset of epiblast progenitor cells (L1epi cells) and then in a subset of primitive endoderm cells (L1dve cells) fated to become DVE. Here we studied how prospective DVE cells are selected. Lefty1 expression in L1epi and L1dve cells depends on Nodal signaling. A cell that experiences the highest level of Nodal signaling begins to express Lefty1 and becomes an L1epi cell. Deletion of Lefty1 alone or together with Lefty2 increased the number of prospective DVE cells. Ablation of L1epi or L1dve cells triggered Lefty1 expression in a subset of remaining cells. Our results suggest that selection of prospective DVE cells is both random and regulated, and that a fixed prepattern for the A–P axis does not exist before the blastocyst stage. Springer Science and Business Media LLC Nature communications Nature Communications 2041-1723 8 1 1492 1492 20171114 10.1038/s41467-017-01625-x 29138408 1360567183419031936 takaoka.katsuyoshi/published_papers/24544465 Katsura Minegishi Masakazu Hashimoto Rieko Ajima Katsuyoshi Takaoka Kyosuke Shinohara Yayoi Ikawa Hiromi Nishimura Andrew P McMahon Karl Willert Yasushi Okada Hiroshi Sasaki Dongbo Shi Toshihiko Fujimori Toshihisa Ohtsuka Yasunobu Igarashi Terry P Yamaguchi Akihiko Shimono Hidetaka Shiratori Hiroshi Hamada A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking. Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a-/-Wnt5b-/- and Sfrp mutant embryos, and also in the presence of a uniform distribution of Wnt5a or Sfrp1, suggesting that Wnt5 and Sfrp proteins act as instructive signals in this process. The absence of planar cell polarity (PCP) core proteins Prickle1 and Prickle2 in individual cells or local forced expression of Wnt5a perturbed polarization of neighboring wild-type cells. Our results suggest that opposing gradients of Wnt5a and Wnt5b and of their Sfrp inhibitors, together with intercellular signaling via PCP proteins, polarize node cells along the anterior-posterior axis for breaking of left-right symmetry. Developmental cell 40 5 439 452 20170313 10.1016/j.devcel.2017.02.010 28292423 takaoka.katsuyoshi/published_papers/51058363 Katsura Minegishi Masakazu Hashimoto Rieko Ajima Katsuyoshi Takaoka Kyosuke Shinohara Yayoi Ikawa Hiromi Nishimura Andrew P. McMahon Karl Willert Yasushi Okada Hiroshi Sasaki Dongbo Shi Toshihiko Fujimori Toshihisa Ohtsuka Yasunobu Igarashi Terry P. Yamaguchi Akihiko Shimono Hidetaka Shiratori Hiroshi Hamada A Wnt5 Activity Asymmetry and Intercellular Signaling via PCP Proteins Polarize Node Cells for Left-Right Symmetry Breaking Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a Elsevier BV Developmental Cell 1534-5807 40 5 439 452.e4 20170300 10.1016/j.devcel.2017.02.010 28292419 1360848657025536640 takaoka.katsuyoshi/published_papers/24544466 Gun-Hee Lee Morihisa Fujita Katsuyoshi Takaoka Yoshiko Murakami Yoshitaka Fujihara Noriyuki Kanzawa Kei-Ichi Murakami Kei-ichi Murakami Eriko Kajikawa Yoko Takada Kazunobu Saito Masahito Ikawa Hiroshi Hamada Yusuke Maeda Taroh Kinoshita A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO. A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRIPTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRYPTIC, a close homologue of CRIPTO, is not sensitive. CRIPTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRIPTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRIPTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior-posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRIPTO shedding. Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRIPTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRYPTIC, a close homologue of CRIPTO, is not sensitive. CRIPTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRIPTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRIPTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior–posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRIPTO shedding. Rockefeller University Press The Journal of cell biology Journal of Cell Biology 1540-8140 215 5 705 718 20161205 10.1083/jcb.201605121 27881714 1050862643878229504 takaoka.katsuyoshi/published_papers/24544467 Julia Wallmeier Hidetaka Shiratori Gerard W Dougherty Gerard W. Dougherty Christine Edelbusch Rim Hjeij Niki T Loges Niki T. Loges Tabea Menchen Heike Olbrich Petra Pennekamp Johanna Raidt Claudius Werner Katsura Minegishi Kyosuke Shinohara Yasuko Asai Katsuyoshi Takaoka Chanjae Lee Matthias Griese Yasin Memari Richard Durbin Anja Kolb-Kokocinski Sascha Sauer John B Wallingford John B. Wallingford Hiroshi Hamada Heymut Omran TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization. TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization Multiprotein complexes referred to as outer dynein arms (ODAs) develop the main mechanical force to generate the ciliary and flagellar beat. ODA defects are the most common cause of primary ciliary dyskinesia (PCD), a congenital disorder of ciliary beating, characterized by recurrent infections of the upper and lower airways, as well as by progressive lung failure and randomization of left-right body asymmetry. Using a whole-exome sequencing approach, we identified recessive loss-of-function mutations within TTC25 in three individuals from two unrelated families affected by PCD. Mice generated by CRISPR/Cas9 technology and carrying a deletion of exons 2 and 3 in Ttc25 presented with laterality defects. Consistently, we observed immotile nodal cilia and missing leftward flow via particle image velocimetry. Furthermore, transmission electron microscopy (TEM) analysis in TTC25-deficient mice revealed an absence of ODAs. Consistent with our findings in mice, we were able to show loss of the ciliary ODAs in humans via TEM and immunofluorescence (IF) analyses. Additionally, IF analyses revealed an absence of the ODA docking complex (ODA-DC), along with its known components CCDC114, CCDC151, and ARMC4. Co-immunoprecipitation revealed interaction between the ODA-DC component CCDC114 and TTC25. Thus, here we report TTC25 as a new member of the ODA-DC machinery in humans and mice. Elsevier BV American journal of human genetics The American Journal of Human Genetics 0002-9297 99 2 460 9 20160804 10.1016/j.ajhg.2016.06.014 27486780 1360565165740174976 takaoka.katsuyoshi/published_papers/24544468 Yasuko Inaba 高岡勝吉 Kyosuke Shinohara Yanick Botilde Ryo Nabeshima Katsuyoshi Takaoka Rieko Ajima Lynda Lamri Hiroyuki Takeda Yumiko Saga Tetsuya Nakamura Hiroshi Hamada Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6. Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6 Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9 + 2 arrangement of microtubules remained normal in Lrrc6(-/-) mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2-IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6(-/-) mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6-dependent mechanism. Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9 + 2 arrangement of microtubules remained normal in Lrrc6‐/‐ mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2–IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6-/- mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6‐dependent mechanism. Wiley Genes to cells : devoted to molecular & cellular mechanisms Gene to cells 1365-2443 21 7 728 39 20160700 10.1111/gtc.12380 27353389 1010282256800726277 takaoka.katsuyoshi/published_papers/24544469 Keisuke Nimura Masamichi Yamamoto Makiko Takeichi Kotaro Saga Katsuyoshi Takaoka Norihiko Kawamura Hirohisa Nitta Hiromichi Nagano Saki Ishino Tatsuya Tanaka Robert J Schwartz Hiroyuki Aburatani Yasufumi Kaneda Regulation of alternative polyadenylation by Nkx2-5 and Xrn2 during mouse heart development. Transcription factors organize gene expression profiles by regulating promoter activity. However, the role of transcription factors after transcription initiation is poorly understood. Here, we show that the homeoprotein Nkx2-5 and the 5'-3' exonuclease Xrn2 are involved in the regulation of alternative polyadenylation (APA) during mouse heart development. Nkx2-5 occupied not only the transcription start sites (TSSs) but also the downstream regions of genes, serving to connect these regions in primary embryonic cardiomyocytes (eCMs). Nkx2-5 deficiency affected Xrn2 binding to target loci and resulted in increases in RNA polymerase II (RNAPII) occupancy and in the expression of mRNAs with long 3'untranslated regions (3' UTRs) from genes related to heart development. siRNA-mediated suppression of Nkx2-5 and Xrn2 led to heart looping anomaly. Moreover, Nkx2-5 genetically interacts with Xrn2 because Nkx2-5(+/-)Xrn2(+/-), but neither Nkx2-5(+/-)nor Xrn2(+/-), newborns exhibited a defect in ventricular septum formation, suggesting that the association between Nkx2-5 and Xrn2 is essential for heart development. Our results indicate that Nkx2-5 regulates not only the initiation but also the usage of poly(A) sites during heart development. Our findings suggest that tissue-specific transcription factors is involved in the regulation of APA. eLife Sciences Publications, Ltd eLife 2050-084X 5 5 e16030 null 20160622 10.7554/eLife.16030 27331609 1570572702870275712 takaoka.katsuyoshi/published_papers/25791825 Inaba Y Shinohara, K Botilde, Y Nabeshima, R Takaoka, K Ajima, R Lamri, L Takeda, H Saga, Y Nakamura, T Hamada, H Transport of outer dynein proteins to ciliary axoneme requires a cytoplasmic protein Lrrc6. Genes to Cells. 21 null null 20160000 10.1111/gtc.12380. takaoka.katsuyoshi/published_papers/25791822 Wallmeier, J Shiratori, H Dougherty, G.W Edelbusch, C Hjeij, R Loges, N.T Menchen, T Olbrich, H Pennekamp, P Raidt, J Werner, C Minegishi, K Shinohara, K Asai, Y Takaoka, K Griese, M Memari, Y Durbin, R Kolb-Kokocinski, A Sauer, S Hamada, H Omran, H TTC25 deficiency results in defects of the outer dynein arm associated machinery and primary ciliary dyskinesia with randomization of left/right body asymmetry. Cell Press Am. J. Hum. Genet. 1537-6605 99 2 460 469 20160000 10.1016/j.ajhg.2016.06.014. 27486780 2-s2.0-84994131605 takaoka.katsuyoshi/published_papers/25791820 Lee, G.H Fujita, M Murakami, Y Takaoka, K Kajikawa, E Kanzawa, N Takada, Y Saito, K Hamada, H Maeda, Y Kinoshita, T PGAP6 sheds a glycosylphosphatidylinositol-anchored protein, CRIPTO, and modulates Nodal signaling. J. Cell Biol. 215 5 705 718 20160000 10.1083/jcb.201605121. takaoka.katsuyoshi/published_papers/26895951 Gun-hee Lee 藤田盛久高岡勝吉村上良子藤原祥高伊川正人濱田博司前田裕輔木下タロウ新規GPI切断酵素であるPGAP6はCRIPTOのnon-cell-autonomousなNodal副受容体機能を起こす null null 20151200 takaoka.katsuyoshi/published_papers/24544470 Gen Shiratsuchi Katsuyoshi Takaoka Tomoko Ashikawa Hiroshi Hamada Daiju Kitagawa RBM14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity. <scp>RBM</scp> 14 prevents assembly of centriolar protein complexes and maintains mitotic spindle integrity Formation of a new centriole adjacent to a pre-existing centriole occurs only once per cell cycle. Despite being crucial for genome integrity, the mechanisms controlling centriole biogenesis remain elusive. Here, we identify RBM14 as a novel suppressor of assembly of centriolar protein complexes. Depletion of RBM14 in human cells induces ectopic formation of centriolar protein complexes through function of the STIL/CPAP complex. Intriguingly, the formation of such structures seems not to require the cartwheel structure that normally acts as a scaffold for centriole formation, whereas they can retain pericentriolar material and microtubule nucleation activity. Moreover, we find that, upon RBM14 depletion, a part of the ectopic centriolar protein complexes in turn assemble into structures more akin to centrioles, presumably by incorporating HsSAS-6, a cartwheel component, and cause multipolar spindle formation. We further demonstrate that such structures assemble in the cytoplasm even in the presence of pre-existing centrioles. This study sheds light on the possibility that ectopic formation of aberrant structures related to centrioles may contribute to genome instability and tumorigenesis. Springer Science and Business Media LLC The EMBO journal The EMBO Journal 1460-2075 34 1 97 114 20150102 10.15252/embj.201488979 25385835 1360848662855676160 takaoka.katsuyoshi/published_papers/24544471 Katsuyoshi Takaoka Hiroshi Hamada Origin of cellular asymmetries in the pre-implantation mouse embryo: a hypothesis. Origin of cellular asymmetries in the pre-implantation mouse embryo: a hypothesis The first cell fate decision during mouse development concerns whether a blastomere will contribute to the inner cell mass (ICM; which gives rise to the embryo proper) or to trophectoderm (TE; which gives rise to the placenta). The position of a cell within an 8- to 16-cell-stage embryo correlates with its future fate, with outer cells contributing to TE and inner cells to the ICM. It remains unknown, however, whether an earlier pre-pattern exists. Here, we propose a hypothesis that could account for generation of such a pre-pattern and which is based on epigenetic asymmetry (such as in histone or DNA methylation) between maternal and paternal genomes in the zygote. The first cell fate decision during mouse development concerns whether a blastomere will contribute to the inner cell mass (ICM; which gives rise to the embryo proper) or to trophectoderm (TE; which gives rise to the placenta). The position of a cell within an 8- to 16-cell-stage embryo correlates with its future fate, with outer cells contributing to TE and inner cells to the ICM. It remains unknown, however, whether an earlier pre-pattern exists. Here, we propose a hypothesis that could account for generation of such a pre-pattern and which is based on epigenetic asymmetry (such as in histone or DNA methylation) between maternal and paternal genomes in the zygote. The Royal Society Philosophical transactions of the Royal Society of London. Series B, Biological sciences Philosophical Transactions of the Royal Society B: Biological Sciences 1471-2970 369 1657 20130536 null 20141205 10.1098/rstb.2013.0536 25349445 1360285709902386176 takaoka.katsuyoshi/published_papers/29633781 Katsuyoshi Takaoka* Establishment of anterior-posterior axis in the mouse embryo Springer Japan New Principles in Developmental Processes 9784431546344 13 26 20141101 10.1007/978-4-431-54634-4_2 2-s2.0-84930892036 takaoka.katsuyoshi/published_papers/24544473 Katsuyoshi Takaoka* Katsuyoshi Takaoka Hiroshi Hamada Cell fate decisions and axis determination in the early mouse embryo. Cell fate decisions and axis determination in the early mouse embryo The mouse embryo generates multiple cell lineages, as well as its future body axes in the early phase of its development. The early cell fate decisions lead to the generation of three lineages in the pre-implantation embryo: the epiblast, the primitive endoderm and the trophectoderm. Shortly after implantation, the anterior-posterior axis is firmly established. Recent studies have provided a better understanding of how the earliest cell fate decisions are regulated in the pre-implantation embryo, and how and when the body axes are established in the pregastrulation embryo. In this review, we address the timing of the first cell fate decisions and of the establishment of embryonic polarity, and we ask how far back one can trace their origins. The mouse embryo generates multiple cell lineages, as well as its future body axes in the early phase of its development. The early cell fate decisions lead to the generation of three lineages in the pre-implantation embryo: the epiblast, the primitive endoderm and the trophectoderm. Shortly after implantation, the anterior-posterior axis is firmly established. Recent studies have provided a better understanding of how the earliest cell fate decisions are regulated in the pre-implantation embryo, and how and when the body axes are established in the pregastrulation embryo. In this review, we address the timing of the first cell fate decisions and of the establishment of embryonic polarity, and we ask how far back one can trace their origins. The Company of Biologists Development (Cambridge, England) Development 1477-9129 139 1 3 14 20120100 10.1242/dev.060095 22147950 1360565169044972800 takaoka.katsuyoshi/published_papers/24544472 Tetsuya Nakamura Daisuke Saito Aiko Kawasumi Kyosuke Shinohara Yasuko Asai Katsuyoshi Takaoka Fenglan Dong Atsuko Takamatsu Jose Antonio Belo Atsushi Mochizuki Hiroshi Hamada Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA. Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA Breaking of left-right symmetry in mouse embryos requires fluid flow at the node, but the precise action of the flow has remained unknown. Here we show that the left-right asymmetry of Cerl2 expression around the node, a target of the flow, is determined post-transcriptionally by decay of Cerl2 mRNA in a manner dependent on its 3' untranslated region. Cerl2 mRNA is absent specifically from the apical region of crown cells on the left side of the node. Preferential decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt-Cerl2 interlinked feedback loops, in which Wnt3 upregulates Wnt3 expression and promotes Cerl2 mRNA decay, whereas Cerl2 promotes Wnt degradation. Mathematical modelling and experimental data suggest that these feedback loops behave as a bistable switch that can amplify in a noise-resistant manner a small bias conferred by fluid flow. Springer Science and Business Media LLC Nature communications Nature Communications 2041-1723 3 1 1322 1322 20120000 10.1038/ncomms2319 23271656 1360283691780039296 takaoka.katsuyoshi/published_papers/24544474 Katsuyoshi Takaoka* Katsuyoshi Takaoka Masamichi Yamamoto Hiroshi Hamada Origin and role of distal visceral endoderm, a group of cells that determines anterior-posterior polarity of the mouse embryo. Origin and role of distal visceral endoderm, a group of cells that determines anterior–posterior polarity of the mouse embryo Anterior-posterior polarity of the mouse embryo has been thought to be established when distal visceral endoderm (DVE) at embryonic day (E) 5.5 migrates toward the future anterior side to form anterior visceral endoderm (AVE). Lefty1, a marker of DVE and AVE, is asymmetrically expressed in implanting mouse embryos. We now show that Lefty1 is expressed first in a subset of epiblast progenitor cells and then in a subset of primitive endoderm progenitors. Genetic fate mapping indicated that the latter cells are destined to become DVE. In contrast to the accepted notion, however, AVE is not derived from DVE but is newly formed after E5.5 from Lefty1(-) visceral endoderm cells that move to the distal tip. Concomitant with DVE migration, all visceral endoderm cells in the embryonic region undergo global movement. In embryos subjected to genetic ablation of Lefty1-expressing DVE cells, AVE was formed de novo but the visceral endoderm including the newly formed AVE failed to migrate, indicating that DVE guides the migration of AVE by initiating the global movement of visceral endoderm cells. Future anterior-posterior polarity is thus already determined by Lefty1(+) blastomeres in the implanting blastocyst. Springer Science and Business Media LLC Nature cell biology Nature Cell Biology 1476-4679 13 7 743 52 20110529 10.1038/ncb2251 21623358 1360565166754280320 takaoka.katsuyoshi/published_papers/24544475 Masayuki Uehara Kenta Yashiro Katsuyoshi Takaoka Masamichi Yamamoto Hiroshi Hamada Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning. Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning The abundance of retinoic acid (RA) is determined by the balance between its synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In particular, the dynamic expression of three CYP26 genes controls the regional level of RA within the body. Pregastrulation mouse embryos express CYP26 but not RALDH. We now show that mice lacking all three CYP26 genes manifest duplication of the body axis as a result of expansion of the Nodal expression domain throughout the epiblast. Mouse Nodal was found to contain an RA-responsive element in intron 1 that is highly conserved among mammals. In the absence of CYP26, maternally derived RA activates Nodal expression in the entire epiblast of pregastrulation embryos via this element. These observations suggest that maternal RA must be removed by embryonic CYP26 for correct Nodal expression during embryonic patterning. The abundance of retinoic acid (RA) is determined by the balance between its synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In particular, the dynamic expression of three CYP26 genes controls the regional level of RA within the body. Pregastrulation mouse embryos express CYP26 but not RALDH. We now show that mice lacking all three CYP26 genes manifest duplication of the body axis as a result of expansion of the Nodal expression domain throughout the epiblast. Mouse Nodal was found to contain an RA-responsive element in intron 1 that is highly conserved among mammals. In the absence of CYP26, maternally derived RA activates Nodal expression in the entire epiblast of pregastrulation embryos via this element. These observations suggest that maternal RA must be removed by embryonic CYP26 for correct Nodal expression during embryonic patterning. Cold Spring Harbor Laboratory Genes & development Genes & Development 1549-5477 23 14 1689 98 20090715 10.1101/gad.1776209 19605690 1361418520491727872 takaoka.katsuyoshi/published_papers/24544476 Masamichi Yamamoto Hideyuki Beppu Katsuyoshi Takaoka Chikara Meno En Li Kohei Miyazono Hiroshi Hamada Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo. Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo The anterior-posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling. The anterior–posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling. Rockefeller University Press The Journal of cell biology Journal of Cell Biology 1540-8140 184 2 323 34 20090126 10.1083/jcb.200808044 19153222 1361137045208877568 takaoka.katsuyoshi/published_papers/24544477 Katsuyoshi Takaoka Masamichi Yamamoto Hiroshi Hamada Origin of body axes in the mouse embryo. Origin of body axes in the mouse embryo How and at what stage of development are the axes of the body determined? The left-right axis of the mouse embryo is generated de novo at embryonic day (E) 8.0 in a manner dependent on pre-existing positional cues. The anterior-posterior (A-P) axis becomes apparent earlier when distally located visceral endoderm migrates toward the future anterior side at E5.5. The direction of this migration is predetermined by asymmetric expression of Lefty1 and Cerl1(Cerberus-like 1). Asymmetric expression of Lefty1 takes place even earlier, in the primitive endoderm of the implanting blastocyst, pushing back the origin of the A-P axis to the peri-implantation stage. Although its functional significance remains to be seen, studies on how this molecular asymmetry emerges may provide insight into the origin of A-P polarity. The first cell fate decision occurs by the morula stage. Although blastomeres at the two-cell or four-cell stage may have biased fates, it is currently unknown whether this bias has any causal relation to later fate. Elsevier BV Current opinion in genetics & development Current Opinion in Genetics & Development 0959-437X 17 4 344 50 20070800 10.1016/j.gde.2007.06.001 17646095 1361981470507345024 takaoka.katsuyoshi/published_papers/24544478 Katsuyoshi Takaoka Masamichi Yamamoto Hidetaka Shiratori Chikara Meno Janet Rossant Yukio Saijoh Hiroshi Hamada The mouse embryo autonomously acquires anterior-posterior polarity at implantation. The Mouse Embryo Autonomously Acquires Anterior-Posterior Polarity at Implantation The earliest recognizable sign of patterning of the mouse embryo along the anteroposterior (A-P) axis is the migration of the distal visceral endoderm (DVE) toward the future anterior side. Here we report an asymmetry in the mouse embryo at an unexpectedly early stage. The gene for Lefty1, a Nodal antagonist that influences the direction of DVE migration, was found to be asymmetrically expressed in the primitive endoderm of the implanting blastocyst. Lefty1 expression begins randomly in the inner cell mass (ICM) of the blastocyst but is regionalized to one side of the tilted ICM shortly after implantation. Asymmetric expression of Lefty1 can be established by in vitro culture, indicating that it does not require interaction with the uterus. The asymmetric Lefty1 expression is induced by Nodal signaling, although Nodal and genes for its effectors are expressed symmetrically. This asymmetry in molecular patterning of the mouse embryo pushes back the origin of the A-P body axis to the peri-implantation stage. Elsevier BV Developmental cell Developmental Cell 1534-5807 10 4 451 9 20060400 10.1016/j.devcel.2006.02.017 16580991 1360574094938070400 takaoka.katsuyoshi/misc/54433141 酒井敬史高岡勝吉渥美颯志郎倉田明咲津川裕司濱田博司篠原恭介 Tppp3は微小管とスフィンゴ脂質を介して,呼吸器繊毛の基底小体の位置の制御と独立性の維持を行う日本分子生物学会年会プログラム・要旨集(Web) 48th null null 20250000 takaoka.katsuyoshi/misc/54433140 高津百花高岡勝吉福谷洋介篠原恭介嗅上皮以外で発現する嗅覚受容体遺伝子ORX1のマウス精子における機能解析日本分子生物学会年会プログラム・要旨集(Web) 48th null null 20250000 takaoka.katsuyoshi/misc/54433139 高岡勝吉マウス着床前胚が発生休止するメカニズム日本分子生物学会年会プログラム・要旨集(Web) 48th null null 20250000 takaoka.katsuyoshi/misc/52000170 高岡勝吉 Mechanism of embryonic diapause during mouse preimplantation マウス着床前の胚休眠のメカニズム【JST機械翻訳】||| 日本解剖学会総会・全国学術集会抄録集(CD-ROM) 130th null null 20250000 takaoka.katsuyoshi/misc/52662231 Ritsuko Nakai Takafumi Yokota Masahiro Tokunaga Mikiro Takaishi Tomomasa Yokomizo Takao Sudo Henyun Shi Yoshiaki Yasumizu Daisuke Okuzaki Chikara Kokubu Sachiyo Tanaka Katsuyoshi Takaoka Ayako Yamanishi Junko Yoshida Hitomi Watanabe Gen Kondoh Kyoji Horie Naoki Hosen Shigetoshi Sano Junji Takeda A Newly Identified Gene Ahed Plays Essential Roles in Murine Hematopoiesis through RNA Splicing BLOOD 1528-0020 144 5614 5615 20241105 10.1182/blood-2024-209978 takaoka.katsuyoshi/misc/49353301 酒井敬史渥美颯志郎高岡勝吉倉田明咲津川裕司濱田博司篠原恭介 Tppp3は微小管を介して気道の運動性繊毛と感覚繊毛の基底小体の位置と繊毛膜の組成を調整する日本分子生物学会年会プログラム・要旨集(Web) 47th null null 20240000 takaoka.katsuyoshi/misc/49353300 村田恵原田哲仁大川恭行廣瀬遙香竹本龍也高岡勝吉マウス着床前胚が発生休止する仕組み日本分子生物学会年会プログラム・要旨集(Web) 47th null null 20240000 takaoka.katsuyoshi/misc/49353299 渥美颯志郎酒井敬史高岡勝吉浜田博司篠原篠原微小管結合因子Tppp3のマウス気管における機能解析日本分子生物学会年会プログラム・要旨集(Web) 47th null null 20240000 takaoka.katsuyoshi/misc/49353298 高岡勝吉マウス胚における発生休止のしくみ日本分子生物学会年会プログラム・要旨集(Web) 47th null null 20240000 takaoka.katsuyoshi/misc/49353297 堂本実咲希安部結高岡勝吉篠原恭介マウスAbitram遺伝子の気管における機能解析日本分子生物学会年会プログラム・要旨集(Web) 47th null null 20240000 takaoka.katsuyoshi/misc/49353288 新規遺伝子AhedはRNAスプライシングを通じて造血に必須な役割を果たす (一社)日本血液学会日本血液学会学術集会 85 34 34 20231000 takaoka.katsuyoshi/misc/49353287 酒井敬史高岡勝吉濱田博司渥美颯志郎篠原恭介マウス嗅上皮における微小管関連タンパク質Tppp3の機能解析 (公社)日本生化学会日本生化学会大会プログラム・講演要旨集 96 [1P 259] 20231000 takaoka.katsuyoshi/misc/49353286 堂本実咲希安部結高岡勝吉篠原恭介マウスAbitram遺伝子の心臓における機能解析 (公社)日本生化学会日本生化学会大会プログラム・講演要旨集 96 [2P 251] 20231000 takaoka.katsuyoshi/misc/49353285 渥美颯志郎酒井敬史高岡勝吉篠原恭介マウス気管における微小管結合タンパク質Tppp3の細胞外部環境の制御における機能解析 (公社)日本生化学会日本生化学会大会プログラム・講演要旨集 96 [2P 262] 20231000 takaoka.katsuyoshi/misc/49353302 村田恵村田恵竹本龍也高岡勝吉 Elucidating of the mechanisms underlying developmental diapause in mouse preimplantation embryos. マウス着床前胚が発生休止する仕組み日本分子生物学会年会プログラム・要旨集(Web) 46th null null 20230000 takaoka.katsuyoshi/misc/49353289 鳥飼純平酒井敬史高岡勝吉濱田博司篠原恭介 Functional analysis of the Tppp3 gene in mouse tracheal epithelial cells マウス気管上皮細胞におけるTppp3遺伝子の機能解析 (公社)日本生化学会 ·(Web) 日本生化学会大会プログラム・講演要旨集 95 1P 157 20221100 takaoka.katsuyoshi/misc/49353303 高岡勝吉 The molecular regulation of embryonic diapause マウス着床前胚が発生休止するしくみ日本分子生物学会年会プログラム・要旨集(Web) 45th null null 20220000 takaoka.katsuyoshi/misc/49353291 酒井敬史高岡勝吉鳥飼純平濱田博司篠原恭介哺乳類の繊毛細胞におけるTppp3の機能解析 (公社)日本生化学会日本生化学会大会プログラム・講演要旨集 94 [P 182] 20211100 takaoka.katsuyoshi/misc/49353290 酒井敬史高岡勝吉鳥飼純平濱田博司篠原恭介 Functional analysis of Tppp3 in mammalian olfactory sensory neurons. 哺乳類の繊毛細胞におけるTppp3の機能解析 (公社)日本生物工学会 ·(Web) 日本生物工学会大会講演要旨集 2021 148 148 20211000 takaoka.katsuyoshi/misc/49353307 浜崎祥生竹本龍也高岡勝吉 Development of tissue-specific lage-scale KO mouse technology 組織特異的かつ大規模ノックアウトマウス作製法の確立とその応用法日本分子生物学会年会プログラム・要旨集(Web) 44th null null 20210000 takaoka.katsuyoshi/misc/49353306 浜崎祥生高岡勝吉 The first cell fate decision in the mouse embryos マウス胚における最初の細胞分化日本分子生物学会年会プログラム・要旨集(Web) 44th null null 20210000 takaoka.katsuyoshi/misc/49353305 鳥飼純平酒井敬史高岡勝吉濱田博司篠原恭介 Functional analysis of mouse Tppp3 gene in tracheal epithelial cells マウスTppp3遺伝子の気管上皮細胞における機能解析日本分子生物学会年会プログラム・要旨集(Web) 44th null null 20210000 takaoka.katsuyoshi/misc/49353304 高岡勝吉脂質異常妊婦の予防医療を目指したマウス胎児における大規模リバースジェネティクス解析かなえ医薬振興財団研究業績集(Web) 49th null null 20200000 takaoka.katsuyoshi/misc/51058334 高岡勝吉哺乳類の卵子と初期胚発生の理解に向けて日本分子生物学会年会プログラム・要旨集(Web) 42nd null null 20190000 takaoka.katsuyoshi/misc/51058332 関嵐川北賢宏高岡勝吉高橋佳子米村重信浜田博司篠原恭介微小管結合因子Tppp3のマウス気管における機能解析日本分子生物学会年会プログラム・要旨集(Web) 41st null null 20180000 takaoka.katsuyoshi/misc/51058331 高岡勝吉マウス胚における前後軸の起源日本分子生物学会年会プログラム・要旨集(Web) 41st null null 20180000 takaoka.katsuyoshi/misc/49353292 高岡勝吉松原健一濱田博司マウス胚発生期における母性Nodalシグナルの役割 (公社)日本生化学会日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88·38 [4T20L 12(3P0931)] 20151200 takaoka.katsuyoshi/misc/51058335 高岡勝吉濱田博司マウス胚における前後軸の起源日本分子生物学会年会プログラム・要旨集(Web) 37th null null 20140000 takaoka.katsuyoshi/misc/49353293 高岡勝吉 ES細胞におけるLeftyの役割本研究では，位置情報獲得機構についての基礎的知見を蓄積し，組織や臓器に合わせた再生医療の多様な方法を生み出すことを目的として，ヒトと同じ哺乳類であるマウスのES細胞がどのように位置情報を獲得するのか検討した．具体的には，ES細胞におけるLefty1,2の役割，特に，胚様体形成やコロニー形成といった位置情報獲得機構における役割に着目し，解析を行った．まず，ES細胞におけるLefty1の発現細胞の位置関係について，蛍光レポーターを用いた遺伝子組換えES細胞で解析した．その結果，単一細胞の際にはLefty1の発現はみられなかったが，数細胞の集団になると1細胞でLefty1が発現を開始し，コロニー形成時にはエッジ部の細胞にのみ発現するという特徴的な発現細胞の挙動を示した(Lefty2については今後同様の解析を行う予定)．次に，ES細胞におけるLefty1,2の機能を明らかにする目的で，Lefty1,2欠損ES細胞を作製し，まずコロニー形成能を調べたところ，野生型ES細胞と同等の形成能を有することが明らかになった． (公財)上原記念生命科学財団上原記念生命科学財団研究報告集 2433-3441 27 1 3 20131200 takaoka.katsuyoshi/misc/51058336 高岡勝吉濱田博司マウス胚における前後軸の起源日本分子生物学会年会プログラム・要旨集(Web) 36th null null 20130000 takaoka.katsuyoshi/misc/49353294 高岡勝吉濱田博司フィードバックループと形づくりマウス胚における前後軸の起源 (公社)日本生化学会日本生化学会大会プログラム・講演要旨集 0037-1017 82 4S17p 3 20090900 takaoka.katsuyoshi/misc/49353296 Rossant Janet 再生・組織形成・器官形成前後軸の起源(Origin of anterior-posterior axis) 日本発生生物学会・日本細胞生物学会日本発生生物学会・日本細胞生物学会合同大会要旨集 40·59 65 65 20070500 takaoka.katsuyoshi/misc/49353295 Li En マウス胚におけるBMP，アクチビン及びExEの関連により確立された遠位臓側内胚葉(Distal Visceral Endoderm is established by the relationship among BMP, ACTIVIN and ExE signaling in the mouse embryo) 日本発生生物学会・日本細胞生物学会日本発生生物学会・日本細胞生物学会合同大会要旨集 40·59 181 181 20070500 takaoka.katsuyoshi/misc/51058333 山本正道別府秀幸高岡勝吉宮園浩平目野主税浜田博司臓側内はい葉のBMPシグナルはDVEの形成及びNodalシグナルの制御をしている．日本分子生物学会年会講演要旨集 28th null null 20050000