Roles of homeobox genes in retinal ganglion cell differentiation and axonal guidance.

In this review, we have described four major families of homeobox genes which play important roles in RGC differentiation as well as axonal pathfinding. The mechanism underlying how these HD TFs affect axonal pathfinding is not entirely known. One possibility is that the downstream targets directly regulated by these HD TF are responsible for axonal guidance. Examples of this are the repression of EphB1 by Isl2, and Vax1/Vax2 regulation of EphB2/EphB3 expression. The roles of Dlx homeobox genes in RGC axonal guidance have not yet been reported. However, in the mouse telencephalon, Dlx1 and Dlx2 promote the tangential migration of GABAergic interneurons by repressing axonal growth (Cobos et al. 2007) and inhibiting Neuropilin-2 expression (Le et al. 2007). It is possible that the genetic program defining RGC identity also encodes a unique "sensory" network for their axons, determining how and where RGC axons respond to guidance cues en route to CNS targets.