Organization of the spina bifida neural tube in Splotch (Pax-3 defective) mouse embryos

The development of the dorsal portion of the spinal cord is adversely affected in a mouse mutant, Splotch (Sp). This mutation is a splicing defect of Pax-3 mRNA, which encodes a transcription factor. Organization of the neural tube in Sp/Sp mice has been studied with the genes Pax-3, Wnt 3a, Msx 1 and Msx 2, which are expressed specifically in the dorsal portion of the neural tube. Regionalization of the Sp neural tube is properly preserved along the dorso-ventral and medio-lateral axes. This suggests that the severe phenotype of the central nervous system (CNS) in Sp embryos is not caused by gross loss of a particular cell population. The level of expression of the Msx 2 gene (a homeobox gene, previously called Hox 8), whose expression pattern is similar to that of Pax-3 in the developing neural tube, is reduced in neuroepithelial cells of Sp mutants in the CNS. This suggests that Msx 2 is located downstream to Pax-3 in a regulatory pathway that is required during the development of the dorsal portion of the neural tube.