Combined activity of the two Gli2 genes of zebrafish play a major role in Hedgehog signaling during zebrafish neurodevelopment.

It has been proposed that the downstream mediator of the evolutionarily conserved Hedgehog pathway Gli2 plays a relatively minor role in neural development of zebrafish. The second gli2 of zebrafish, gli2b, is expressed in the neural plate and the central nervous system. Our comparative analysis of the developmental role of gli2/gli2b demonstrate a major role of the two Gli2s in mediating Hh signaling. The Gli2s play an early Hh-independent repressor role in the maintenance of neural progenitors and an Hh-dependent activating role during cell differentiation in the floor plate, branchial motor neurons, and sensory neurons. Our analysis of Gli2b loss-of-function using antisense morpholino oligonucleotides indicates that the functions of the two Gli2s diverged in evolution. Gli2b acts in cell proliferation and plays an early role in the hindbrain within a regulatory cascade involving Notch and Ngn1, as well as a role as specific activator in rhombomere 4.