ALTERED CELL-PROLIFERATION IN THE SPINAL-CORD OF MOUSE NEURAL-TUBE MUTANTS CURLY TAIL AND PAX3 SPLOTCH-DELAYED

The mutant mouse strains splotch-delayed (Pax3(Sp-d)) and curly tail ( ct) develop neural tube defects (NTDs) in the lumbosacral region of th e neuraxis. Some research has focused on cell proliferation around the time of posterior neuropore closure in these mutants; however, there are little data on the effects of NTDs on cell birth at later stages o f development. To investigate the role neural tube closure might play in cytogenesis of the spinal cord, the thymidine analog 5-bromo-2'-deo xyuridine (BrdU) was injected into pregnant splotch-delayed and curly tail mice at various stages of gestation. The mean number of labelled cells in the dorsal and ventral halves of spina bifida and control emb ryos was then calculated per section and per mm(2). Mutagenically sepa rated PCR (MS-PCR), was used to ascertain the genotype of splotch-dela yed embryos. Our data indicate that the peak proliferation dates, for both the dorsal and ventral regions of the cord, are similar in spina bifida and control embryos. However, the quantity of proliferation is significantly different between affected and unaffected embryos. In ge neral, there are markedly fewer cells born in spina bifida embryos in early neural tube development, followed by a short period of equal pro liferation, and culminating in a significant increase in cell prolifer ation later in gestation. This increase in proliferation results in a greater number of cells being born in spina bifida embryos compared to controls. Several possible explanations for this phenomenon are consi dered, including the hypothesis that the roof plate, or other factors induced by neural tube closure, might have an anti-mitotic activity. ( C) 1997 Elsevier Science B.V.