RT Journal Article SR Electronic T1 Bsh coordinates neuronal fate specification with synaptic connectivity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.01.462699 DO 10.1101/2021.10.01.462699 A1 Xu, Chundi A1 Ramos, Tyler A1 Doe, Chris Q. YR 2021 UL http://biorxiv.org/content/early/2021/10/01/2021.10.01.462699.abstract AB It is widely accepted that neuronal fate is initially determined by spatial and temporal cues acting in progenitors, followed by transcription factors (TFs) that act in post-mitotic neurons to specify their functional identity (e.g. ion channels, cell surface molecules, and neurotransmitters). It remains unclear, however, whether a single TF can coordinately regulate both steps. The five lamina neurons (L1-L5) in the Drosophila visual system, are an ideal model for addressing this question. Here we show that the homeodomain TF Brain-specific homeobox (Bsh) is expressed in a subset of lamina precursor cells (LPCs) where it specifies L4 and L5 fate, and suppresses homeodomain TF Zfh1 to prevent L1 and L3 fate. Subsequently, in L4 neurons, Bsh initiates a feed forward loop with another homeodomain TF Apterous (Ap) to drive recognition molecule DIP-β expression, which is required for precise L4 synaptic connectivity. We conclude that a single homeodomain TF expressed in both precursors and neurons can coordinately generate neuronal fate and synaptic connectivity, thereby linking these two developmental events. Furthermore, our results suggest that acquiring LPC expression of a single TF, Bsh, may be sufficient to drive the evolution of increased brain complexity.Competing Interest StatementThe authors have declared no competing interest.