Spred-2 Suppresses Aorta-Gonad-Mesonephros Hematopoiesis by Inhibiting MAP Kinase Activation

Ikuo Nobuhisa, Reiko Kato, Hirofumi Inoue, Makiko Takizawa, Keisuke Okita, Akihiko Yoshimura, Tetsuya Taga

研究成果: Article

47 引用 (Scopus)

抄録

In midgestation mouse embryos, the aorta-gonad-mesonephros (AGM) region generates hematopoietic stem cells and definitive hematopoiesis is regulated by cell-cell interaction and signaling molecules. We showed that a Ras/mitogen-activated protein (MAP) kinase signaling-specific inhibitor and a dominant negative mutant Ras blocked the production of CD45+ hematopoietic cells in embryonic day 11.5 AGM culture, indicating an essential role for the MAP kinase pathway in AGM hematopoiesis. Overexpression of the Ras/MAP kinase pathway regulator, Spred-2, in the AGM culture significantly reduced the number of CD45+ cells. In contrast, production of CD45+ cells from the AGM region of Spred-2-null mice was up-regulated as compared with wild-type littermates. Furthermore, Spred-2-deficient mice exhibited elevated hematopoietic colony formation from vascular endothelial-cadherin+ cells. These data indicate that Spred-2 functions as a negative regulator of AGM hematopoiesis by inhibiting hematopoietic cytokine signaling.

元の言語English
ページ(範囲)737-742
ページ数6
ジャーナルJournal of Experimental Medicine
199
発行部数5
DOI
出版物ステータスPublished - 2004 3 1
外部発表Yes

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Mesonephros
Hematopoiesis
Gonads
Mitogen-Activated Protein Kinases
Aorta
Hematopoietic Stem Cells
Cell Communication
Embryonic Structures
Endothelial Cells
Cell Count
Cytokines

ASJC Scopus subject areas

  • Immunology

これを引用

Spred-2 Suppresses Aorta-Gonad-Mesonephros Hematopoiesis by Inhibiting MAP Kinase Activation. / Nobuhisa, Ikuo; Kato, Reiko; Inoue, Hirofumi; Takizawa, Makiko; Okita, Keisuke; Yoshimura, Akihiko; Taga, Tetsuya.

:: Journal of Experimental Medicine, 巻 199, 番号 5, 01.03.2004, p. 737-742.

研究成果: Article

Nobuhisa, Ikuo ; Kato, Reiko ; Inoue, Hirofumi ; Takizawa, Makiko ; Okita, Keisuke ; Yoshimura, Akihiko ; Taga, Tetsuya. / Spred-2 Suppresses Aorta-Gonad-Mesonephros Hematopoiesis by Inhibiting MAP Kinase Activation. :: Journal of Experimental Medicine. 2004 ; 巻 199, 番号 5. pp. 737-742.
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AU - Taga, Tetsuya

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