Involvement of Ath3 in CNTF-mediated differentiation of the late retinal progenitors

The cellular diversity of the mammalian retina is underpinned by multipotential neural progenitors that generate retinal neurons and glia with temporal and spatial specificity. It is thought, based on studies using a variety of approaches, that the fate of retinal progenitors is determined through interactions between temporally and spatially arrayed epigenetic cues with intrinsic factors that regulate the competence of cells to respond to such cues. Here, we demonstrate interactions between an intrinsic factor Ath3, a neural bHLH protein, and an extrinsic factor CNTF during the differentiation of the late retinal progenitors along the bipolar cell lineage. Expression of Ath3 is predominantly associated with the late stage of retinal histogenesis when bipolar cells are specified, and in adult it is detected in cells expressing bipolar cell-specific markers. We demonstrate that CNTF-induced bipolar cell differentiation is accompanied by an increase in levels of Ath3 transcripts and compromised when Ath3 expression is attenuated. Our study suggests that the influence of CNTF on the differentiation of late retinal progenitors is mediated through Ath3.