An important role of endothelial hairy-related transcription factors in mouse vascular development.

• Material Type: 博士論文
• Title: An important role of endothelial hairy-related transcription factors in mouse vascular development.
• Author/Editor: Morioka, Takashi; Sakabe, Masahide; Ioka, Tomoko; Iguchi, Tomoko; Mizuta, Ken; Hattammaru, Miwa; Sakai, Chihiro; Itoh, Munehiro; Sato, Genki E.; Hashimoto, Aya; Fujita, Masahide; Okumura, Kazuki; Araki, Mutsumi; Xin, Mei; Pedersen, Roger A.; Utset, Manuel F.; Kimura, Hiroshi; Nakagawa, Osamu
• Author Heading: Morioka, Takashi; Sakabe, Masahide; Ioka, Tomoko; Iguchi, Tomoko; Mizuta, Ken; Hattammaru, Miwa; Sakai, Chihiro; Itoh, Munehiro; Sato, Genki E.; Hashimoto, Aya; Fujita, Masahide; Okumura, Kazuki; Araki, Mutsumi; Xin, Mei; Pedersen, Roger A.; Utset, Manuel F.; Kimura, Hiroshi; Nakagawa, Osamu
• Publication, Distribution, etc.: Wiley
• Publication Date: 2014-11
• Publication Date (W3CDTF): 2014-11
• Alternative Title: 内皮細胞におけるHrt転写調節因子の血管形態形成に対する意義
• Periodical title: Genesis
• No. or year of volume/issue: 52 11
• Volume: 52
• Issue: 11
• Pages: 897-906
• ISSN (Periodical Title): ISSN : 1526-954X
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2015-03-16
• Dissertation Number: 乙第1352号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: mouse embryo; vascular morphogenesis; Hrt/Hey; Robo4; Src family kinases
• Target Audience: 一般
• Note (General): type:Article; The Hairy-related transcription factor family of Notch- and ALK1-downstream transcriptional repressors, called Hrt/Hey/Hesr/Chf/Herp/Gridlock, has complementary and indispensable functions for vascular development. While mouse embryos null for either Hrt1/Hey1 or Hrt2/Hey2 did not show early vascular phenotypes, Hrt1/Hey1; Hrt2/Hey2 double null mice (H1ko/H2ko) showed embryonic lethality with severe impairment of vascular morphogenesis. It remained unclear, however, whether Hrt/Hey functions are required in endothelial cells or vascular smooth muscle cells. In this study, we demonstrate that mice with endothelial-specific deletion of Hrt2/Hey2 combined with global Hrt1/Hey1 deletion (H1ko/H2eko) show abnormal vascular morphogenesis and embryonic lethality. Their defects were characterized by the failure of vascular network formation in the yolk sac, abnormalities of embryonic vascular structures and impaired smooth muscle cell recruitment, and were virtually identical to the H1ko/H2ko phenotypes. Among signaling molecules implicated in vascular development, Robo4 expression was significantly increased and activation of Src family kinases was suppressed in endothelial cells of H1ko/H2eko embryos. The present study indicates an important role of Hrt1/Hey1 and Hrt2/Hey2 in endothelial cells during early vascular development, and further suggests involvement of Robo4 and Src family kinases in the mechanisms of embryonic vascular defects caused by the Hrt/Hey deficiency.; 博士（医学）・乙第1352号・平成27年3月16日; © 2014 Wiley Periodicals, Inc.; 発行元が定める登録猶予期間終了の後、本文を登録予定（2015.11）; identifier:Genesis Vol.52 No.11 p.897-906; identifier:1526954X; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2969; identifier:Genesis, 52(11): 897-906
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2969/1/01%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2969/2/02%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/2969/6/03%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1002/dvg.22825
• Periodical Title (NCID): AA1143089X; https://ci.nii.ac.jp/ncid/AA1143089X
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU