@article {68279, title = {Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity}, journal = {eLife}, year = {2024}, month = {2024 Jan 05}, abstract = {

The brain generates diverse neuron types which express unique homeodomain transcription factors (TFs) and assemble into precise neural circuits. Yet a mechanistic framework is lacking for how homeodomain TFs specify both neuronal fate and synaptic connectivity. We use\ Drosophila\ lamina neurons (L1-L5) to show the homeodomain TF Brain-specific homeobox (Bsh) is initiated in lamina precursor cells (LPCs) where it specifies L4/L5 fate and suppresses homeodomain TF Zfh1 to prevent L1/L3 fate. Subsequently, Bsh activates the homeodomain TF Apterous (Ap) in L4 in a feedforward loop to express the synapse recognition molecule DIP-β, in part by Bsh direct binding a\ DIP-β\ intron. Thus, homeodomain TFs function hierarchically: primary homeodomain TF (Bsh) first specifies neuronal fate, and subsequently acts with secondary homeodomain TF (Ap) to activate DIP-β, thereby generating precise synaptic connectivity. We speculate that hierarchical homeodomain TF function may represent a general principle for coordinating neuronal fate specification and circuit assembly.

}, doi = {10.7554/eLife.90133}, url = {https://doi.org/10.7554/eLife.90133}, author = {Chundi Xu and Tyler B. Ramos and Ed M. Rogers and Michael B. Reiser and Chris Q. Doe} }