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

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2969-2980
Number of pages12
JournalMolecular and Cellular Biology
Volume23
Issue number8
DOIs
Publication statusPublished - 2003 Apr
Externally publishedYes

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Gastrulation
Bone Morphogenetic Protein 4
Thymus Gland
Dwarfism
Lymphopenia
Mesonephros
Gonads
Mesoderm
Thymocytes
Osteogenesis
Aorta
Complementary DNA
Phosphorylation
Parturition
T-Lymphocytes
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Nosaka, T., Morita, S., Kitamura, H., Nakajima, H., Shibata, F., Morikawa, Y., ... Kitamura, T. (2003). Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. Molecular and Cellular Biology, 23(8), 2969-2980. https://doi.org/10.1128/MCB.23.8.2969-2980.2003

Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. / Nosaka, Tetsuya; Morita, Sumiyo; Kitamura, Hidetomo; Nakajima, Hideaki; Shibata, Fumi; Morikawa, Yoshihiro; Kataoka, Yuki; Ebihara, Yasuhiro; Kawashima, Toshiyuki; Itoh, Tsuneo; Ozaki, Katsutoshi; Senba, Emiko; Tsuji, Kohichiro; Makishima, Fusao; Yoshida, Nobuaki; Kitamura, Toshio.

In: Molecular and Cellular Biology, Vol. 23, No. 8, 04.2003, p. 2969-2980.

Research output: Contribution to journalArticle

Nosaka, T, Morita, S, Kitamura, H, Nakajima, H, Shibata, F, Morikawa, Y, Kataoka, Y, Ebihara, Y, Kawashima, T, Itoh, T, Ozaki, K, Senba, E, Tsuji, K, Makishima, F, Yoshida, N & Kitamura, T 2003, 'Mammalian twisted gastrulation is essential for skeleto-lymphogenesis', Molecular and Cellular Biology, vol. 23, no. 8, pp. 2969-2980. https://doi.org/10.1128/MCB.23.8.2969-2980.2003
Nosaka T, Morita S, Kitamura H, Nakajima H, Shibata F, Morikawa Y et al. Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. Molecular and Cellular Biology. 2003 Apr;23(8):2969-2980. https://doi.org/10.1128/MCB.23.8.2969-2980.2003
Nosaka, Tetsuya ; Morita, Sumiyo ; Kitamura, Hidetomo ; Nakajima, Hideaki ; Shibata, Fumi ; Morikawa, Yoshihiro ; Kataoka, Yuki ; Ebihara, Yasuhiro ; Kawashima, Toshiyuki ; Itoh, Tsuneo ; Ozaki, Katsutoshi ; Senba, Emiko ; Tsuji, Kohichiro ; Makishima, Fusao ; Yoshida, Nobuaki ; Kitamura, Toshio. / Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. In: Molecular and Cellular Biology. 2003 ; Vol. 23, No. 8. pp. 2969-2980.
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