Broad promotes neuroepithelial stem cell differentiation in the drosophila optic lobe

Abstract

Brain development requires the generation of the right number, and type, of neurons and glial cells at the right time. The Drosophila optic lobe, like mammalian brains, develops from simple neuroepithelia; they first divide symmetrically to expand the progenitor pool and then differentiate into neuroblasts, which divide asymmetrically to generate neurons and glial cells. Here, we investigate the mechanisms that control neuroepithelial growth and differentiation in the optic lobe. We find that the Broad/Tramtrack/ Bric a brac-zinc finger protein Broad, which is dynamically expressed in the optic lobe neuroepithelia, promotes the transition of neuroepithelial cells to medulla neuroblasts. Loss of Broad function causes neuroepithelial cells to remain highly proliferative and delays neuroepithelial cell differentiation into neuroblasts, which leads to defective lamina and medulla. Conversely, Broad overexpression induces neuroepithelial cells to prematurely transform into medulla neuroblasts. We find that the ecdysone receptor is required for neuroepithelial maintenance and growth, and that Broad expression in neuroepithelial cells is repressed by the ecdysone receptor. Our studies identify Broad as an important cell-intrinsic transcription factor that promotes the neuroepithelial-cell-to-neuroblast transition.