Sustained expression of <i>unc-4</i> homeobox gene and <i>unc-37/Groucho</i> in postmitotic neurons specifies the spatial organization of the cholinergic synapses in <i>C. elegans</i>.

Abstract

Neuronal cell fate determinants establish the identities of neurons by controlling gene expression to regulate neuronal morphology and synaptic connectivity. However, it is not understood if neuronal cell fate determinants have postmitotic functions in synapse pattern formation. Here we identify a novel role for UNC-4 homeobox protein and its corepressor UNC-37/Groucho, in tiled synaptic patterning of the cholinergic motor neurons in <i>Caenorhabditis elegans</i>. We show that <i>unc-4</i> is not required during neurogenesis but is required in the postmitotic neurons for proper synapse patterning. In contrast, <i>unc-37</i> is required in both developing and postmitotic neurons. The synaptic tiling defects of <i>unc-4</i> mutants are suppressed by <i>bar-1/β-catenin</i> mutation, which positively regulates the expression of <i>ceh-12/HB9</i>. Ectopic <i>ceh-12</i> expression partly underlies the synaptic tiling defects of <i>unc-4</i> and <i>unc-37</i> mutants. Our results reveal a novel postmitotic role of neuronal cell fate determinants in synapse pattern formation through inhibiting the canonical Wnt signaling pathway.