Regulation of Sonic hedgehog signaling during CNS development

Sonic hedgehog (Shh) is a requisite component of a signaling pathway essential for the establishment of patterns of growth and differentiation in many tissues during embryonic development. Within the central nervous system (CNS), Shh is implicated in specifying diverse neuronal fates derived from the ventral portion of the neural tube. For Shh to carry out its role as an inductive signal it must be expressed in the correct tissues at the appropriate developmental stage as well as at a suitable level. The regulation of the Shh gene is critical for proper CNS development as loss of one allele in humans or two alleles in mice result in structural defects of the nervous system including holoprosencephaly. In contrast, the over activation of the Shh signaling pathway has been implicated in the formation of a number of tumors including medulloblastomas and basal cell carcinomas. These findings suggest that Shh signaling must be maintained under tight regulatory control. Studies performed in my laboratory use combinations of molecular and genetic techniques to identify the genes that regulate Shh signaling during CNS development in the mouse. Understanding the multifaceted manner by which Shh signaling is controlled will further elucidate the molecular mechanisms contributing to congenital abnormalities and tumor formation that result from its misregulation.