Human oocytes fertilized in fallopian tubes are transported and implanted at the endometrium. For around ten months, implanted embryos develop and grow in utero with the support of exchanges of gases and nutrients between mothers and fetuses until birth. Many mysteries about the developmental processes of fetuses and the necessary intrauterine environment are remained to be elucidated. Why do major causes of infertility such as implantation failure and early miscarriage take place? As about 5% of newborns have some congenital malformations such as neural tube defects or heart diseases, mechanisms for the development of these congenital anomalies are also still unclear. To dissect the intrauterine environment necessary for embryo implantation and subsequent development and identify genetic factors causing congenital diseases, we are exploiting mice as an experimental model animal. Mice are powerful tools in which both reverse and forward genetics can be readily applicable. As a genetic approach for congenital malformations, we are generating several mouse models, in which human disease-related genes are mutated. As for the uterine environment, we are analyzing mechanical factors of the uterus such as smooth muscle contractions and endometrial stiffness utilizing biophysical techniques in combination with in vitro culture of embryos. These approaches can accelerate basic biological research on embryonic development as well as the evaluation of therapeutics by allowing us to dissect functions of genetic pathways and intrauterine properties for embryo implantation and development.
|Chief Scientist||Chihara Kimura-Yoshida,Ph.D.|
|Research Fellow||Kyoko Mochida|
|Training Researcher||Misuzu Okuno|
|Administrative Staff||Chihiro Matsuno
Isao Matsuo, Chiharu Kimura-Yoshida and Yoko Ueda
Developmental and mechanical roles of Reichert’s membrane in mouse embryos
Philos Trans R Soc Lond B Biol Sci. 377, 20210257 (2022)
Chiharu Kimura-Yoshida, Kyoko Mochida, Shin-Ichiro Kanno and Isao Matsuo
USP39 is essential for mammalian epithelial morphogenesis through upregulation of planar cell polarity components.
Communications Biology 55(1): 378 (2022)
Mami Tsume-Kajioka, Chiharu Kimura-Yoshida, Kyoko Mochida, Yoko Ueda, and Isao Matsuo
BET proteins are essential for specification and maintenance of the epiblast lineage in mouse preimplantation embryos.
BMC Biology 20(1): 64 (2022)
Isao Matsuo, Chiharu Kimura-Yoshida
Identification of Cell Autonomous and Non-Cell Autonomous Functions of Heparan Sulfate Glycosaminoglycan Chains by Creating Chimeric Mouse Embryos.
Methods Mol Biol. 2303: 579-593 (2022)
Yoko Ueda, Chiharu Kimura-Yoshida, Kyoko Mochida, Mami Tsume, Yoshitaka Kameo, Taiji Adachi, Olivier Lefebvre, Ryuji Hiramatsu and Isao Matsuo
Intrauterine pressures adjusted by Reichert’s membrane are crucial for early mouse morphogenesis.
Cell Reports 31, 107637 (2020)
Yu Kitadate, David J. Jörg, Moe Tokue, Ayumi Maruyama, Rie Ichikawa, Soken Tsuchiya, Eri Segi-Nishida, Toshinori Nakagawa, Aya Uchida, Chiharu Kimura-Yoshida, Seiya Mizuno, Fumihiro Sugiyama, Takuya Azami, Masatsugu Ema, Chiyo Noda, Satoru Kobayashi, Isao Matsuo, Yoshiakira Kanai, Takashi Nagasawa, Yukihiko Sugimoto, Satoru Takahashi, Benjamin D. Simons, Shosei Yoshida
Competition for mitogens regulates spermatogenic stem cell homeostasis in an open niche
Cell Stem Cell 24, 79-92 (2019)
Chiharu Kimura-Yoshida, Kyoko Mochida, Masa-aki Nakaya, Takeomi Mizutani and Isao Matsuo
Cytoplasmic localization of GRHL3 upon epidermal differentiation triggers cell shape change for epithelial morphogenesis
Nature Communications 9(1), 4059 (2018)
Isao Matsuo and Ryuji Hiramatsu
Mechanical perspectives on the anterior-posterior axis polarization of mouse implanted embryos
Mechanisms of Development 144 (PtA), 62-70 (2017)
Hidenori Nishihara, Naoki Kobayashi, Chiharu Kimura-Yoshida, Kuo Yanc, Olga Grishinac, Qiong Dinga, Akiko Nakanishi, Takeshi Sasaki, Mika Hirakawa, Kenta Sumiyama, Yasuhide Furuta, Victor Tarabykin, Isao Matsuo, Norihiro Okada
Coordinately co-opted multiple transposable elements constitute an enhancer for wnt5a expression in the mammalian secondary palate
PLOS Genetics (2016) 12(10):e1006380.
Chiharu Kimura-Yoshida, Kyoko Mochida, Kristina Ellwanger, Christof Niehrs, and Isao Matsuo
Fate specification of neural plate border by canonical Wnt and Grhl3 is crucial for neural tube closure
EBioMedicine 2, 513-527 (2015)
Isao Matsuo and Chiharu Kimura-Yoshida
Extracellular distribution of diffusible growth factors controlled by heparin sulfate proteoglycans during mammalian embryogenesis
Philos Trans R Soc Lond B Biol Sci. 369, 20130545 (2014)
Ryuji Hiramatsu, Toshiki Matsuoka, Chiharu Kimura-Yoshida, Sung-Woong Han, Kyoko Mochida, Taiji Adachi, Shuichi Takayama and Isao Matsuo
External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos
Developmental Cell 27, 131-144 (2013)
Isao Matsuo and Chiharu Kimura-Yoshida
Extracellular modulation of Fibroblast Growth Factor signaling through heparan sulfate proteoglycans in mammalian development
Current Opinion in Genetics & Development 23, 399-407 (2013)
Makiko Iwafuchi-Doi, Kazunari Matsuda, Kazuhiro Murakami, Hitoshi Niwa, Paul J. Tesar, Jun Aruga, Isao Matsuo, and Hisato Kondoh
Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells
Development 139, 3926-3937 (2012)
Mami Tsume, Chiharu Kimura-Yoshida, Kyoko Mochida, Yukinao Shibukawa,Saori Amazaki, Yoshinao Wada, Ryuji Hiramatsu, Kayo Shimokawa, and Isao Matsuo
Brd2 is required for cell cycle exit and neuronal differentiation through the E2F1 pathway in mouse neuroepithelial cells.
Biochem. Biophys. Res. Commun. 425, 762-768 (2012)
Kayo Shimokawa*, Chiharu Kimura-Yoshida*, Naoko Nagai, Kazuhiro Mukai, Kazumi Matsubara, Hideto Watanabe, Yoichi Matsuda, Kyoko Mochida and Isao Matsuo (* Co-1st authors)
Cell surface heparan sulfate chains regulate local reception of FGF signaling in the mouse embryo
Developmental Cell 21, 257-272 (2011)
Daniel Diaczok, Sara DiVall, Isao Matsuo, Fredric E. Wondisford, Andrew M. Wolfe and Sally Radovick
Deletion of Otx2 in GnRH Neurons results in a mouse model of hypogonadotropic Hypogonadism.
Molecular Endocrinology 25, 833-846 (2011)
Ryuji Hiramatsu, Kyoko Harikae, Naoki Tsunekawa, Masamichi Kurohmaru, Isao Matsuo and Yoshiakira Kanai FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation.
Development 137, 303-312 (2010)
Shinichi Miyagawa, Anne Moon, Ryuma Haraguchi, Chie Inoue, Masayo Harada, Chiaki Nakahara, Kentaro Suzuki, Daisuke Matsumaru, Takehito Kaneko, Isao Matsuo, Lei Yang, Makoto M. Taketo, Taisen Iguchi, Sylvia M. Evans, and Gen Yamada Dosage-dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program.
Development 136, 3969-3978 (2009)
Sayaka Sugiyama, Ariel A Di Nardo, Shinichi Aizawa, Isao Matsuo, Michel Volovitch, Alain Prochiantz and Takao K Hensch Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity.
Cell 134, 508-520 (2008)
Takeshi Sasaki, Hidenori Nishihara, Mika Hirakawa, Koji Fujimura, Mikiko Tanaka, Nobuhiro Kokubo, Chiharu Kimura-Yoshida, Isao Matsuo, Kenta Sumiyama, Naruya Saitou, Tomomi Shimogori and Norihiro Okada Possible involvement of SINEs in mammalian-specific brain formation.
Proc. Natl. Acad. Sci. USA 105, 4220-4225 (2008)
Chieko Koike, Akihiro Nishida, Shinji Ueno, Hiromitsu Saito, Rikako Sanuki, Shigeru Sato, Akiko Furukawa, Shinichi Aizawa, Isao Matsuo, Noboru Suzuki, Mineo Kondo, and Takahisa Furukawa Functional roles of Otx2 transcription factor in postnatal mouse retinal development .
Mol. Cell. Biol. 27, 8318-8329 (2007)
Shigeru Sato, Tatsuya Inoue, Koji Terada, Isao Matsuo, Shinichi Aizawa, Yasuo Tano, Takashi Fujikado and Takahisa Furukawa.
Dkk3-Cre BAC transgenic mouse line: A tool for highly-efficient deletion in retinal progenitor cells.
Genesis 45, 502-507 (2007)
Chiharu Kimura-Yoshida, E Tian, Hiroshi Nakano, Saori Amazaki, Kayo Shimokawa, Janet Rossant, Shinichi Aizawa and Isao Matsuo.
Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes.
Proc. Natl. Acad. Sci. USA Vol.104 5919-5924(2007)
Chiharu Kimura-Yoshida, Hiroshi Nakano, Daiji Okamura, Kazuki Nakao, Shigenobu Yonemura, Jose A.Belo, Shinichi Aizawa, Yasuhisa Matsui and Isao Matsuo.
Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm.
Developmental Cell 9, 639-650(2005)
Izumi Oda-Ishii, Vincent Bertrand, Isao Matsuo, Patrick Lemaire and Hidetoshi Saiga
Making very similar embryos with divergent genomes: conservation of regulatory mechanisms of Otx between the ascidians Halocynthia roretzi and Ciona intertinalis.
Development 132, 1663-1673 (2005)
Daisuke Kurokawa, Hiroshi Kiyonari, Rika Nakayama, Chiharu Kimura-Yoshida, Isao Matsuo and Shinichi Aizawa
Regulation of Otx2 expression and its functions in mouse forebrain and midbrain.
Development 131, 3319-3331 (2004)
Daisuke Kurokawa, Nobuyuki Takasaki, Hiroshi Kiyonari, Rika Nakayama, Chiharu Kimura-Yoshida, Isao Matsuo and Shinichi Aizawa
Regulation of Otx2 expression and its functions in mouse epiblast and anterior neuroectoderm.
Development 131, 3307-3317 (2004)
Chiharu Kimura-Yoshida, Kuniko Kitajima, Izumi Oda-Ishii, E Tian, Misao Suzuki, Masayuki Yamamoto, Tohru Suzuki, Makoto Kobayashi, Shinichi Aizawa and Isao Matsuo
Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for the vertebrate head specification.
Development 131, 57-71 (2004)
Akihiro Nishida, Akiko Furukawa, Chieko Koike, Yasuo Tano, Shinichi Aizawa, Isao Matsuo and Takahisa Furukawa
Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development.
Nature Neuroscience 6, 1255-1263 (2003)
Takuichiro Hide, Jun Hatakeyama, Chiharu Kimura, E Tian, Naoki Takeda, Yukitaka Ushio, Toshihiko Shiroishi, Shinichi Aizawa and Isao Matsuo
Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice.
Development 129, 4347-4357 (2002)
E Tian, Chiharu Kimura, Naoki Takeda, Shinichi Aizawa and Isao Matsuo
Otx2 is required to respond to signals from anterior neural ridge for forebrain specification.
Developmental Biology 242, 204-223 (2002)
Yoko Suda, Zakir Hossain, Chiyoko Kobayashi, Osamu Hatano, Michio Yoshida, Isao Matsuo and Shinichi Aizawa
Emx2 directs the development of diencephalon in cooperation with Otx2.
Development 128, 2433-2450 (2001)
Chiharu Kimura, Michael M. Shen, Naoki Takeda, Shinichi Aizawa and Isao Matsuo
Complementary functions between Otx2 and Cripto in initial patterning of mouse epiblast.
Developmental Biology 235, 12-32 (2001)
Kenryo Furushima, Takuya Murata, Isao Matsuo and Shinichi Aizawa
A new murine zinc finger gene, Opr.
Mechanisms of Development 98, 161-164 (2000)
Chiharu Kimura, Kazuya Yoshinaga, E Tian, Misao Suzuki, Shinichi Aizawa and Isao Matsuo
Visceral endoderm mediates forebrain development by suppressing posteriorizing signals.
Developmental Biology 225, 304-321 (2000)
Takahiro Nakano, Takuya Murata, Isao Matsuo and Shinichi Aizawa
OTX2 directly interacts with LIM1 and HNF-3beta.
Biochem. Biophys. Res. Commun. 267, 64-70 (2000)
Yoko Suda, Jun Nakabayashi, Isao Matsuo and Shinichi Aizawa
Functional equivalency between Otx2 and Otx1 in development of rostral head.
Development 126, 743-757 (1999)
Yoko Suda, Isao Matsuo and Shinichi Aizawa
Cooperation between Otx1 and Otx2 genes in developmental patterning of rostral brain.
Mechanisms of Development 69, 125-141 (1997)
Chiharu Kimura, Naoki Takeda, Misao Suzuki, Mitsuo Oshimura, Shinichi Aizawa and Isao Matsuo
Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells.
Development 124, 3929-3941 (1997)
Mitsuru Oyanagi, Isao Matsuo, Yuichi Wakabayashi, Shinichi Aizawa and Ryo Kominami
Mouse homeobox-containing gene Otx2, maps to mouse Chromosome 14.
Mammalian Genome 8, 292-293 (1997)
Isao Matsuo, Yoko Suda, Michio Yoshida, Tatsuya Ueki, Chiharu Kimura, Shigeru Kuratani and Shinichi Aizawa
Otx and Emx functions in patterning of the vertebrate rostral head.
Cold Spring Harbor Symposia on Quantitative Biology, Cold Spring Harbor Laboratory Press, Volume LXII, 545-553 (1997)
Michio Yoshida, Yoko Suda, Isao Matsuo, Norimasa Miyamoto, Naoki Takeda, Shigeru Kuratani and Shinichi Aizawa
Emx1 and Emx2 functions in development of dorsal telencephalon.
Development 124, 101-111 (1997)
Shigeru Kuratani, Isao Matsuo and Shinichi Aizawa
Developmental patterning and evolution of the mammalian viscerocranium: Genetic insights into comparative morphology.
Developmental Dynamics 209, 1-17 (1997)
Norimasa Miyamoto, Michio Yoshida, Shigeru Kuratani, Isao Matsuo and Shinichi Aizawa
Defects of urogenital development in mice lacking Emx2.
Development 124, 1653-1664 (1997)
Yoko Suda, Isao Matsuo, Shigeru Kuratani and Shinichi Aizawa
Otx1 function overlaps with Otx2 in development of mouse forebrain and midbrain.
Genes to Cells 1, 1031-1044 (1996)
Isao Matsuo, Shigeru Kuratani, Chiharu Kimura, Naoki Takeda, and Shinichi Aizawa
Mouse Otx2 functions in the formation and patterning of rostral head.
Genes & Development 9, 2646-2658 (1995)
T. Tsukada, Y. Tomooka, S. Takai, Y. Ueda, S. Nishikawa, T. Yagi, T. Tokunaga, N. Takeda, Y. Suda, S. Abe, I. Matsuo, Y. Ikawa and S. Aizawa
Enhanced proliferative potential in culture of cells from p53-defecient mice.
Oncogene 8, 3313-3322 (1993)
Isao Matsuo, Msayuki Takeuchi and Kunio Yasuda
Identification of the contact sites of a factor that interacts with motif I (alphaCEI) of the chicken alphaA-crystallin lens-specific enhancer.
Biochem. Biophys. Res. Commun. 184, 24-30 (1992)
Isao Matsuo and Kunio Yasuda
The cooperative interaction between two motifs of an enhancer element of the chicken alphaA-crystallin gene, alphaCE1 and alphaCE2, confers lens-specific expression.
Nucleic Acids Research 20, 3701-3712 (1992)
Isao Matsuo, Masahi Kitamura, Kenji Okazaki and Kunio Yasuda
Binding of a factor to an enhancer element responsible for the tissue-specific expression of the alphaA-crystallin gene.
Development 113, 539-550 (1990)
Isao Matsuo, Ph.D.
Department of Molecular Embryology
Osaka Medical Center for Maternal and Child Health 840 Murodo-cho, Izumi, Osaka 594-1101, Japan
E-mail: imatsuo @
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