Serotonin signaling via 5-HT3A alters development of sacral neural crest derivatives that innervate the lower urinary tract

The autonomic nervous system is derived from the neural crest and supplies motor innervation to the smooth muscle of visceral organs, including the lower urinary tract (bladder and urethra, LUT). In rodents, autonomic innervation of the LUT is supplied by the major pelvic ganglia (PG) that lie near the neck of the bladder and proximal urethra. Compared to other autonomic ganglia, the PG are unique in that they harbor both sympathetic and parasympathetic neurons. The coordinated activity of PG neurons is critical for normal functioning of the LUT – however, surprisingly little is known about how PG neuronal diversity is established or what molecular factors control PG development. In this study we conducted transcriptome profiling of Sox10-H2BVenus+ sacral neural crest (NC) progenitors to discover candidate genes involved in PG neurogenesis. The long term study goal is to create an encyclopedia of genes that participate in regulating formation of innervation in the lower urogenital tract. Neuronal progenitors that derive from the neural crest have been isolated based on their expression of a Sox10-H2BVenus transgene (C3Fe.Tg(Sox10-HIST2H2BE/Venus)ASout) and their transcriptional profiles determined by hybridization to mouse microarrays with essentially complete genome coverage to quantitate expression levels of genes in FACS isolated populations.