Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis

  1. Lydie Pani1,2,
  2. Melissa Horal1, and
  3. Mary R. Loeken1,2,3
  1. 1Section on Cellular and Molecular Physiology, Joslin Diabetes Center, 2Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA

Abstract

Pax-3 is a transcription factor that is expressed in the neural tube, neural crest, and dermomyotome. We previously showed that apoptosis is associated with neural tube defects (NTDs) in Pax-3-deficient Splotch (Sp/Sp) embryos. Here we show that p53 deficiency, caused by germ-line mutation or by pifithrin-α, an inhibitor of p53-dependent apoptosis, rescues not only apoptosis, but also NTDs, in Sp/Sp embryos. Pax-3 deficiency had no effect on p53 mRNA, but increased p53 protein levels. These results suggest that Pax-3 regulates neural tube closure by inhibiting p53-dependent apoptosis, rather than by inducing neural tube-specific gene expression.

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Footnotes

  • 3 Corresponding author.

  • E-MAIL mary.loeken{at}joslin.harvard.edu; FAX (617) 732-2541.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.969302.

    • Received December 12, 2001.
    • Accepted January 31, 2002.
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