Ataxin-2 binding protein 1 is a context-specific positive regulator of Notch signaling during neurogenesis in Drosophila melanogaster

Abstract

The role of Notch pathway during lateral inhibition underlying binary cell fate choice is extensively studied, although context-specificity that generates diverse outcomes is relatively less well understood. In the peripheral nervous system of Drosophila melanogaster, differential Notch signaling between cells of proneural cluster orchestrates sensory organ specification. Here we report functional analysis of Drosophila Ataxin2 binding protein1 (dA2BP1) during this process. It’s human orthologue A2BP1 is linked to type 2 Spinocerebellar ataxia and other complex neuronal disorders. Downregulation of dA2BP1 in the proneural cluster increases adult sensory bristle number whereas it’s over-expression results in loss of bristles. We show that dA2BP1 regulates sensory organ specification by potentiating Notch signaling. Supporting its direct involvement, the biochemical analysis shows that dA2BP1 is part of the Suppressor of Hairless (Su(H)) complex both in the presence and absence of Notch. However, in the absence of Notch signaling, the dA2BP1 interacting fraction of Su(H) does not associate with the repressor proteins, Groucho and CtBP. Based on these data we propose a model explaining requirement of dA2BP1 as a positive regulator of Notch, whose activity is context-specific.