Subfunctionalization of tbx2 paralogues during photoreceptor cell specification in zebrafish.

Zebrafish possess three distinct sources of retinal progenitors that produce identical photoreceptor subtypes throughout life. All photoreceptor progenitors simultaneously express multiple transcription factors specifying different identities, requiring mechanisms to repress alternative fates. Disruption of the tbx2 paralogues, tbx2a or tbx2b , resulted in a cell-fate switch of sws1 cones into rods. Here, we demonstrate that tbx2b was necessary for sws1 cone differentiation during embryogenesis and outgrowth at the retinal margin, but tbx2a was necessary during photoreceptor regeneration. Transgenic overexpression of Tbx2b was not sufficient to drive the sws1 cone fate or sws1 opsin expression. Rather, Tbx2b repressed the synergistic activity of Nrl and Crx at the rhodopsin promoter. Targeting the transcription factor thrβ2 on wildtype and tbx2 mutant backgrounds revealed a hierarchy wherein early progenitors have the potential to be respecified from lws cones into sws1 cones or rods. But late progenitors are limited to either the sws1 cone or rod fate. These data support a model in which transcriptional repressors, like tbx2a and tbx2b, orchestrate progression through competency states.