Pax-3 regulates neurogenesis in neural crest-derived precursor cells

The peripheral nervous system consists of multiple neural lineages derived from the neural crest (NC), Pax-3 is expressed in the NC and when mutated i n the splotch mouse (Sp) results in the loss of derivatives from this precu rsor cell population, We have investigated the role of Pax-3 in regulating the generation of neurons from NC-derived precursor cells in vitro. Pax-3 m RNA in NC cultures is initially expressed in all NC but is subsequently onl y retained in neurons, suggesting a role in their generation. To determine whether Pax-3 is involved in neuron development, we first examined the gene ration of sensory-like neurons in NC cultures from Sp mice. Fivefold less s ensory-like neurons were generated in NC cultures from Sp homozygous mice a s compared to wild-type littermates. The role of Pax-3 in sensory neuron ge neration was then directly examined in dorsal root ganglia cultures by down -regulating the expression of Pax-3 protein with antisense oligonulceotides , It was found that antisense oligonulceotides inhibited 80-90% of newly ge nerated sensory neurons; however, there was no significant effect on the su rvival of sensory neurons or the precursor population. These results sugges t that Pax-3 has a role in regulating the differentiation of peripheral neu rons. (C) 1999 Wiley-Liss,Inc.