The emergent design of the neural tube: prepattern, SHH morphogen and GLI code

The Sonic hedgehog (Shh) pathway plays an important role in the development of many tissues and organs. The secreted ligand Shh has been shown to act as a mitogen, morphogen and survival factor in different contexts whereas the three Gli transcription factors act as Shh mediators in a context-dependent combinatorial fashion. The common wisdom has been that Gli protein function is subject to Shh signaling. One can ask how Gli proteins act and what the nature of Shh signaling during CNS dorsal-ventral patterning is. Is it possible that Hedgehog signals are only one of several ways to regulate Gli activity? Moreover, in light of the partial rescue of the neural tube phenotype of Shh or Smoothened mutant embryos in Shh(-/-);Gli3(-/-), Smoothened(-/-);Gli3(-/-), and Shh(-/-);Rab23(-/-) double null embryos, one can consider the roles that the Shh-Gli pathway may have taken to orchestrate congruent prepattern and growth, and the importance of creating the correct number of precursors in patterning mechanisms.