BHLH Genes and Retinal Cell Fate Specification

Abstract

The various cell types in the vertebrate retina arise from a pool of common progenitors. The way that the cell types are specified has been a long-standing issue. Decades of research have yielded a large body of information regarding the involvement of extrinsic factors, and only recently has the function of intrinsic factors begun to emerge. This article reviews recent studies addressing the role of basic helix-loop-helix (bHLH) factors in specifying retinal cell types, with an emphasis on bHLHhierarchies leading to photoreceptor production. Photoreceptor genesis appears to employ two transcriptional pathways: ngn2-->neuroD-->raxL and ath5-->neuroD-->raxL. ngn2 and ath5 function in progenitors, which can potentially develop into different cell types. neuroD represents one of the central steps in photoreceptor specification. Ath5 is also essential for ganglion cell development. It remains to be demonstrated whether a bHLH gene functions as a key player in specifying the other types of retinal cells. Genetic knockout studies have indicated intricate cross-regulation among bHLH genes. Future studies are expected to unveil the mechanism by which bHLH factors network with intrinsic factors and communicate with extrinsic factors to ensure a balanced production of the various types of retinal cells.