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Understanding the role of neuronal cell fate determinants in synapse pattern formation in C. elegans Kurashina, Mizuki


Animal locomotion and behaviour are ultimately controlled by the precise neuronal circuit formation at the level of synaptic connection. Mutations in the genes that specify individual neuronal cell fate (or cell fate determinants) alter synaptic connections and circuit wiring which results in the malfunction of the nervous system. It is however not fully understood if the defects in these mutants are merely due to a consequence of cell fate transformation, or the cell fate determinants have specific functions in synapse pattern formation. Here we identify a novel role for a homeobox transcription factor UNC-4 and its co-repressor UNC-37/Groucho, in tiled synapse pattern formation of the cholinergic motor neurons (DA8 and DA9) in Caenorhabditis elegans. In unc-4 and unc-37 mutant animals, we observed large overlap between the synaptic domains of DA8 and DA9. Strikingly, we show using temperature-sensitive mutants and auxin-inducible degron system that unc-4 is not required during embryonic development when DA neurons cell fate is set but is required post-embryonically. In contrast, unc-37 is required embryonically and post-embryonically in DA neurons for a tiled synaptic innervation. Our result reveals a novel post-cell fate determination role of homeobox gene in neuronal pattern formation.

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