miR-7 Buffers Differentiation in the Developing Drosophila Visual System

Abstract

The 40,000 neurons of the medulla, the largest visual processing center of the $\textit{Drosophila}$ brain, derive from a sheet of neuroepithelial cells. During larval development, a wave of differentiation sweeps across the neuroepithelium, converting neuroepithelial cells into neuroblasts that sequentially express transcription factors specifying different neuronal cell fates. The switch from neuroepithelial cells to neuroblasts is controlled by a complex gene regulatory network and is marked by the expression of the proneural gene $\textit{l’sc}$. We discovered that microRNA $\textit{miR-7}$ is expressed at the transition between neuroepithelial cells and neuroblasts. We showed that $\textit{miR-7}$ promotes neuroepithelial cell-to-neuroblast transition by targeting downstream Notch effectors to limit Notch signaling. $\textit{miR-7}$ acts as a buffer to ensure that a precise and stereotypical pattern of transition is maintained, even under conditions of environmental stress, echoing the role that $\textit{miR-7}$ plays in the eye imaginal disc. This common mechanism reflects the importance of robust visual system development.