栗原裕基|iBMath

	教授
	栗原裕基
	Professor Hiroki Kurihara
	所属：	東京大学大学院医学系研究科分子細胞生物学専攻代謝生理化学分野教授
	専門分野：	循環器病学、発生生物学

研究概要

当研究室では、頭頚部の形態形成や心臓発生、血管新生、初期胚発生を中心に、生命の「かたちづくり」を制御する分子メカニズムの解明に取り組んでいます。生物の多様な形態のなかでも、血管が作る樹状構造は最も魅力的なテーマの１つです。私たちはこれまで、in vitro血管新生モデルの経時的イメージングにより、細胞が追い越しあったり行きつ戻りつしながら相互の位置関係を変えていく複雑な集団運動によって、全体的に樹状構造が形成されていくことを発見しました。これは、特別の形質を獲得した先端細胞が血管新生を先導し、茎細胞がそれに後続するという従来の考え方とは異なるものでした。それでは、一見不規則な細胞集団の動きが樹状構造という見事なパターンを生み出す背景にはどのようなロジックが隠されているのでしょうか？こうした多様な細胞の動態は、細胞の表現型を規定する遺伝子転写制御機構とどのようにリンクしているのでしょうか？こうした問題を解明するために、本拠点において数理科学分野の研究者とともに理論と実験の双方向的な研究を進めています。

原著論文

Kitazawa T, Takechi M, Hirasawa T, Adachi N, Narboux-Nême N, Kume H, Maeda K, Hirai T, Miyagawa-Tomita S, Kurihara Y, Hitomi J, Levi G, Kuratani S, Kurihara H. Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids. Nat. Commun. 6:6853, 2015.
Kitazawa T, Fujisawa K, Narboux-Nême N, ArimA Y, Kawamura Y, Inoue T, Wada Y, Kohro T, Aburatani H, Kodama T, Kim K-S, Sato T, Uchijima Y, Maeda K, Miyagawa-Tomita S, Minoux M, Rijli FM, Levi G, Kurihara Y, Kurihara H. Distinct effects of Hoxa2 overexpression in cranial neural crest populations reveal that the mammalian hyomandibular-ceratohyal boundary maps within the styloid process. Dev. Biol. 402:162-174, 2015.
Kim K-S, Arima Y, Kitazawa T, Nishiyama K, Asai R, Uchijima Y, Sato T, Levi G, Kitanaka S, Igarashi T, Kurihara Y, Kurihara H. Endothelin regulates neural crest deployment and fate to form great vessels through Dlx5/Dlx6-independent mechanisms. Mech. Dev. 130:553-566, 2013.
Arima Y, Miyagawa-Tomita S, Maeda K, Asai R, Seya D, Minoux M, Rijli FM, Nishiyama K, Kim KS, Uchijima Y, Ogawa H, Kurihara Y, Kurihara H. Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling. Nat. Commun. 3:1267, 2012.
Arima S, Nishiyama K, Ko T, Arima Y, Hakozaki Y, Sugihara K, Koseki H, Uchijima Y, Kurihara Y, Kurihara H. Angiogenic morphogenesis driven by dynamic and heterogeneous collective endothelial cell movement. Development 138:4763-76, 2011.
Tonami K, Kurihara Y, Arima S, Nishiyama K, Uchijima Y, Asano T, Sorimachi H, Kurihara H. Calpain 6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1. J. Cell Sci. 124:1214-1223, 2011.
Kawamura Y, Uchijima Y, Horike N, Tonami K, Nishiyama K, Amano T, Asano T, Kurihara Y, Kurihara H. Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrest. J. Clin. Invest. 120:2817-2828, 2010.
Asai R, Kurihara Y, Fujisawa K, Sato T, Kawamura Y, Kokubo H, Tonami K, Nishiyama K, Uchijima Y, Miyagawa-Tomita S, Kurihara H. Endothelin receptor type-A expression defines a distinct cardiac subdomain within the heart field, with a later implication of this signaling pathway in chamber myocardium formation. Development 137:3823-3833, 2010.
Sato T, Kawamura Y, Asai R, Amano T, Uchijima Y, Dettlaff-Swiercz DA, Offermanns S, Kurihara Y, Kurihara H. Recombinase-mediated cassette exchange revealed the selective use of Gq/G11-dependent and -independent endothelin-1/endothelin type-A receptor signaling in pharyngeal arch development. Development 135:755-765, 2008.
Sato T, Kurihara Y, Asai R, Kawamura Y, Tonami K, Uchijima Y, Heude E, Ekker M, Levi G, Kurihara H. An endothelin-1 switch specifies maxillomandibular identity. Proc. Natl. Acad. Sci. U. S. A. 105:18806-18811, 2008.
Kurihara Y, Kawamura Y, Uchijima Y, Amano T, Kobayashi H, Asano T, Kurihara H. Maintenance of genomic methylation patterns during preimplantation development requires the somatic form of DNA methyltransferase 1. Dev. Biol. 313:335-346, 2008.
Tonami K, Kurihara Y, Aburatani H, Uchijima Y, Asano T, Kurihara H. Calpain 6 is involved in microtubule stabilization and cytoskeletal organization. Mol. Cell. Biol. 27:2548-2561, 2007.
Ozeki H, Kurihara Y, Tonami K, Watatani S, Kurihara H. Endothelin-1 regulates the dorsoventral branchial arch patterning in mice. Mech. Dev. 121:387-395, 2004
Oh-hashi Y, Shindo T, Kurihara Y, Imai T, Wang Y, Morita H, Imai Y, Kayaba Y, Nishimatsu H, Suematsu Y, Hirata Y, Yazaki Y, Nagai R, Kuwaki T, Kurihara H. Elevated sympathetic nervous activity in mice deficient in αCGRP. Circ. Res. 89:983-990, 2001.
Shindo T, Kurihara Y, Nishimatsu H, Moriyama N, Kakoki M, Wang Y, Imai Y, Ebihara A, Kuwaki T, Ju K-H, Minamino N, Kangawa K, Ishikawa T, Fukuda M, Akimoto Y, Kawakami H, Imai Y, Imai T, Morita H, Yazaki Y, Nagai R, Hirata Y, Kurihara H. Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene. Circulation 104:1964-1971, 2001.
Shindo T, Kurihara H, Kuno K, Yokoyama H, Wada T, Kurihara Y, Imai T, Wang Y, Ogata M, Oh-hashi Y, Morita H, Ishikawa T, Nagai R, Yazaki Y, Matsushima K. ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility and organ morphology and function. J. Clin. Invest. 105:1345-1352, 2000.
Kurihara Y, Kurihara H, Morita H, Cao W-H, Ling G-Y, Kumada M, Kimura S, Nagai R, Yazaki Y, Kuwaki T. Role of endothelin-1 in stress response in the central nervous system. Am. J. Physiol. 279:R515-R521, 2000.
Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T, Yazaki Y. Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J. Clin. Invest. 96:293-300, 1995.
Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R, Oda H, Kuwaki T, Cao W-H, Kamada N, Jishage K, Ouchi Y, Azuma S, Toyoda Y, Ishikawa T, Kumada M, Yazaki Y. Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature 368:703-710, 1994.
Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411-415, 1988.