Pax3 acts cell autonomously in the neural tube and somites by controlling cell surface properties.
Pax3 is a member of the paired-box-containing transcription factors. It is expressed in the developing somites, dorsal spinal cord, mesencephalon and neural crest derivatives. Several loss-of-function mutations are correlated with the Splotch phenotype in mice and Waardenburg syndrome in humans. Malformations include a lack of muscle in the limb, a failure of neural tube closure and dysgenesis of numerous neural crest derivatives. In this study we have used embryonic stem (ES) cells to generate a lacZ knock-in into the Pax3 locus. The Pax3 knock-in Splotch allele (Sp(2G)) was used to generate Pax3-deficient ES cells in order to investigate whether, in chimeric embryos, Pax3 is acting cell autonomously in the somites and the neural tube. We found that while Pax3 function is essential for the neuroepithelium and somites, a wild-type environment rescues mutant neural crest cells. In the two affected embryonic tissues, mutant and wild-type cells undergo segregation and do not intermingle. The contribution of mutant cells to the neural tube and the somites displayed temporal differences. All chimeric embryos showed a remarkable contribution of blue cells to the neural tube at all stages analyzed, indicating that the Pax3-deficient cells are not excluded from the neural epithelium while development proceeds. In contrast, this is not true for the paraxial mesoderm. The somite contribution of Pax3(-/-) ES cells becomes less frequent in older embryos as compared to controls with Pax3(+/-) ES cells. We propose that although Pax3 function is related to cell surface properties, its role may differ in various tissues. In fact, apoptosis was found in Pax3-deficient cells of the lateral dermomyotome but not in the neural tube.
Mansouri
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Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg 11, D-37077 Göttingen, Germany. amansou@gwdg.de
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Larue
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D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology*; D009831:Olfactory Mucosa / Q000166:cytology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D019170:Somites / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse