Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis.
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-alpha, 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.
Pani
Lydie
L
Section on Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Horal
Melissa
M
Loeken
Mary R
MR
D000818:Animals; D017209:Apoptosis; D052160:Benzothiazoles; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D016158:Genes, p53; D005838:Genotype; D006579:Heterozygote; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009432:Neural Crest / Q000196:embryology; D009436:Neural Tube Defects / Q000235:genetics*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors; D014050:Toluene / Q000031:analogs & derivatives / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D052160:Benzothiazoles; D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D013844:Thiazoles; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C068686:Pax3 protein, mouse; D014050:Toluene; C121565:pifithrin