Embryonic retinal progenitor cells are heterogeneic with respect to proneural transcription factor expression

In all species that have been studied, the first cell type in the retina to differentiate is the retinal ganglion cell (RGC). We are specifically interested in understanding how these first neurons arise from the progenitor pool, since there is no predecessor neuron to influence their fate. The current model of retinogenesis proposes that the integration of extrinsic signals, transcriptional regulators and intercellular interactions are necessary for the differentiation of retinal progenitor cells into the various types of retinal neurons and glia. Evidence suggests that individual members of the proneural basic helix-loop-helix (bHLH) family of transcriptional regulators are critical for the proper acquisition of particular retinal cellular identities, yet evidence also suggests that combinations of bHLH's are necessary for other cellular identities. We hypothesize that subsets of proneural genes are expressed within discrete cell types. We have used in situ hybridizations combined with subsequent immunolabeling for progenitor cells and RCCs to determine which members of the proneural bHLH transcription factors are expressed in mitotically active progenitor cells and/or differentiating RGCs. Our results demonstrate that even early in retinal development, members of this family of transcription factors are differentially expressed, with some genes restricted to progenitor cells and some to newborn RGCs. Our results also suggest that the progenitor pool itself consists of subpopulations of progenitors that express different proneural bHLH genes. Finally, we have analyzed a previously uncharacterized member of this family, chicken acheate-achute homolog 3 (Cash3), during retinal development.