Mammalian twisted gastrulation is essential for skeleto-lymphogenesis

Tetsuya Nosaka, Sumiyo Morita, Hidetomo Kitamura, Hideaki Nakajima, Fumi Shibata, Yoshihiro Morikawa, Yuki Kataoka, Yasuhiro Ebihara, Toshiyuki Kawashima, Tsuneo Itoh, Katsutoshi Ozaki, Emiko Senba, Kohichiro Tsuji, Fusao Makishima, Nobuaki Yoshida, Toshio Kitamura

研究成果: Article査読

74 被引用数 (Scopus)

抄録

Dorsoventral patterning depends on the local concentrations of the morphogens. Twisted gastrulation (TSG) regulates the extracellular availability of a mesoderm inducer, bone morphogenetic protein 4 (BMP-4). However, TSG function in vivo is still unclear. We isolated a TSG cDNA as a secreted molecule from the mouse aorta-gonad-mesonephros region. Here we show that TSG-deficient mice were born healthy, but more than half of the neonatal pups showed severe growth retardation shortly after birth and displayed dwarfism with delayed endochondral ossification and lymphopenia, followed by death within a month. TSG-deficient thymus was atrophic, and phosphorylation of SMAD1 was augmented in the thymocytes, suggesting enhanced BMP-4 signaling in the thymus. Since BMP-4 promotes skeletogenesis and inhibits thymus development, our findings suggest that TSG acts as both a BMP-4 agonist in skeletogenesis and a BMP-4 antagonist in T-cell development. Although lymphopenia in TSG-deficient mice would partly be ascribed to systemic effects of runtiness and wasting, our findings may also provide a clue for understanding the pathogenesis of human dwarfism with combined immunodeficiency.

本文言語English
ページ(範囲)2969-2980
ページ数12
ジャーナルMolecular and cellular biology
23
8
DOI
出版ステータスPublished - 2003 4月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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