ANALYSIS OF NEURAL CREST CELL-MIGRATION IN SPLOTCH MICE USING A NEURAL CREST-SPECIFIC LACZ REPORTER

Studies on the mouse Splotch (Sp) mutation, a deletion in the transcri ption factor Pax-3, have revealed that Pax-3 is essential for normal d evelopment of the neural crest. We have investigated the defect in neu ral crest development using a Wnt-1::LacZ reporter construct to mark n eural crest cells. Staining embryos for p-galactosidase activity at di fferent developmental stages revealed a severe reduction in the number of neural crest cells which emigrated from the neural tube at the vag al and rostral trunk levels. At the caudal thoracic, lumbar, and sacra l levels there was a complete loss of neural crest cell emigration. In contrast to previous work in culture, we saw no evidence for any dela y in the onset of neural crest cell migration at anterior levels. Pax- 3 is expressed in the dorsal neural tube, where the neural crest cells originate, in migrating neural crest cells, and in semitic cells alon g the migratory pathway. Hence, it is not clear which aspect of the Pa x-3 expression accounts for the observed phenotype. We addressed this problem by transplanting neural tissue between mouse and chick embryos . Our studies indicate that the defect in the Splotch mutation is not intrinsic to the neural crest cells themselves, but appears to reflect inappropriate cell interactions either within the neural tube or betw een the neural tube and the somite. (C) 1997 Academic Press.