Involvement of Mash1 in EGF-mediated regulation of differentiation in the vertebrate retina

It is believed that signaling through the epidermal growth factor (EGF) receptor plays a critical role in the development of Drosophila eyes. In the present study we have analyzed the role that EGF-mediated signaling plays in vertebrate retinal development. We have observed that during late retinal neurogenesis EGF delays rod photoreceptor differentiation and that this effect of EGF involves the modulation of expression of a homologue of Drosophila proneural genes, Mash1. EGF causes a significant decrease in Mash1 expression and an increase in the proportion of proliferating cells in the retina in vitro. The decrease in Mash1 expression is accompanied by a concomitant decrease in opsin expression, a marker for overt rod photoreceptor differentiation. Withdrawal of EGF leads to an increase in both Mash1 and opsin expression; however, the onset of expression of Mash1 precedes that of opsin. Our study identifies a proliferative intermediate precursor, characterized by Mash1 expression, that is the target of EGF- mediated suppression of rod photoreceptor differentiation. Based on the evolutionarily conserved roles of EGF- and Notch-mediated signaling in the delay of differentiation in proliferating precursors we propose that these distinct signaling mechanisms act in concert to ensure the fidelity of the strict temporal and spatial nature of cell fate determination in the retina.