Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis
- Lydie Pani1,2,
- Melissa Horal1, and
- Mary R. Loeken1,2,3
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.
Keywords
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.
- Cold Spring Harbor Laboratory Press