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, R M alformations 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 th e Pax3 locus. The Pax3 knock-in Splotch allele (Sp(2G)) was used to generat e Pax3-deficient ES cells in order to investigate whether, in chimeric embr yos, Pax3 is acting cell autonomously in the somites and the neural tube. W e found that while Pax3 function is essential for the neuroepithelium and s omites, a wild-type environment rescues mutant neural crest cells. In the t wo affected embryonic tissues, mutant and wild-type cells undergo segregati on and do not intermingle. The contribution of mutant cells to the neural tube and the somites display ed temporal differences, All chimeric embryos showed a remarkable contribut ion of blue cells to the neural tube at all stages analyzed, indicating tha t the Pax3-deficient cells are not excluded from the neural epithelium whil e development proceeds. In contrast, this is not true for the paraxial meso derm, The somite contribution of Pax3(-/-) ES cells becomes less frequent i n older embryos as compared to controls with Pan3(+/-) ES cells. We propose that although Pax3 function is related to cell surface properties, its rol e may differ in various tissues, In fact, apoptosis was found in Pax3-defic ient cells of the lateral dermomyotome but not in the neural tube.