Sonic hedgehog signaling in the developing CNS where it has been and where it is going

Sonic Hedgehog (Shh) is one of three mammalian orthologs of the Hedgehog (Hh) family of secreted proteins first identified for their role in patterning the Drosophila embryo. In this review, we will highlight some of the outstanding questions regarding how Shh signaling controls embryonic development. We will mainly consider its role in the developing mammalian central nervous system (CNS) where the pathway plays a critical role in orchestrating the specification of distinct cell fates within ventral regions, a process of exquisite complexity that is necessary for the proper wiring and hence function of the mature system. Embryonic development is a process that plays out in both the spatial and the temporal dimensions, and it is becoming increasingly clear that our understanding of Shh signaling in the CNS is grounded in an appreciation for the dynamic nature of this process. In addition, any consideration of Hh signaling must by necessity include a consideration of data from many different model organisms and systems. In many cases, the extent to which insights gained from these studies are applicable to the CNS remains to be determined, yet they provide a strong framework in which to explore its role in CNS development. We will also discuss how Shh controls cell fate diversification through the regulation of patterned target gene expression in the spinal cord, a region where our understanding of the morphogenetic action of graded Shh signaling is perhaps the furthest advanced.