An unexpected bifurcation in the Pointed transcriptional effector network contributes specificity and robustness to retinal cell fate acquisition

Spatiotemporally specific and robust cell fate transitions are fundamental to the development of appropriately patterned tissues. In the Drosophila retina, receptor tyrosine kinase / mitogen activated protein kinase (MAPK) signaling acts through the transcriptional effector Pointed (Pnt) to direct two distinct rounds of photoreceptor specification. A relay mechanism between two Pnt isoforms, a MAPK responsive form PntP2 and a constitutively active form PntP1, initiates and sustains the transcriptional response. Here, we report an unexpected bifurcation in the Pnt effector network. We show that PntP2 works redundantly with a closely related but previously uncharacterized isoform, PntP3, to activate pntP1 during specification of first round photoreceptors. Intrinsic activity differences between PntP2 and PntP3, combined with positive and negative transcriptional auto- and cross-regulation, buffer first-round fates against conditions of low signaling. In contrast, in a mechanism that may be adaptive to the stronger signaling environment used to specify second round fates, PntP2 uniquely activates pntP1 . We propose that differences in expression patterns, transcriptional activities and regulatory interactions between Pnt isoforms together facilitate context-appropriate cell fate specification in different signaling environments.