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First published online July 21, 2003
doi: 10.1242/10.1242/dev.00615

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Development 130, 3929-3939 (2003)
Copyright © 2003 The Company of Biologists Limited

Interplay between the tumor suppressor p53 and TGFß signaling shapes embryonic body axes in Xenopus

Kimiko Takebayashi-Suzuki1,*, Jun Funami1,*, Daisuke Tokumori1,*, Akira Saito2, Tetsuro Watabe2, Kohei Miyazono2, Akifumi Kanda1 and Atsushi Suzuki1,{dagger}

1 Institute for Amphibian Biology, Hiroshima University Graduate School of Science, Kagamiyama 1-3-1, Higashi-Hiroshima 739-8526, Japan
2 Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

{dagger} Author for correspondence (e-mail: asuzuki{at}hiroshima-u.ac.jp)

Accepted 13 May 2003

The transcription factor p53 has been shown to mediate cellular responses to diverse stresses such as DNA damage. However, the function of p53 in cellular differentiation in response to growth factor stimulations has remained obscure. We present evidence that p53 regulates cellular differentiation by modulating signaling of the TGFß family of growth factors during early Xenopus embryogenesis. We show that p53 functionally and physically interacts with the activin and bone morphogenetic protein pathways to directly induce the expression of the homeobox genes Xhox3 and Mix.1/2. Furthermore, functional knockdown of p53 in embryos by an antisense morpholino oligonucleotide reveals that p53 is required for the development of dorsal and ventral mesoderm. Our data illustrate a pivotal role of interplay between the p53 and TGFß pathways in cell fate determination during early vertebrate embryogenesis.

Key words: Axis formation, TGFß, p53, Xenopus, Embryogenesis




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