Sustained expression of unc-4 homeobox gene and unc-37/Groucho in postmitotic neurons specifies the spatial organization of the cholinergic synapses in C. elegans
Mizuki Kurashina,
Jane Wang,
Jeffrey Lin,
Kathy Kyungeun Lee,
Arpun Johal,
Kota Mizumoto
Affiliations
Mizuki Kurashina
Department of Zoology, University of British Columbia, Vancouver, Canada; Graduate Program in Cell and Developmental Biology, University of British Columbia, Vancouver, Canada
Jane Wang
Department of Zoology, University of British Columbia, Vancouver, Canada
Jeffrey Lin
Department of Zoology, University of British Columbia, Vancouver, Canada
Kathy Kyungeun Lee
Department of Zoology, University of British Columbia, Vancouver, Canada
Arpun Johal
Department of Zoology, University of British Columbia, Vancouver, Canada
Department of Zoology, University of British Columbia, Vancouver, Canada; Graduate Program in Cell and Developmental Biology, University of British Columbia, Vancouver, Canada; Life Sciences Institute, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
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 Caenorhabditis elegans. We show that unc-4 is not required during neurogenesis but is required in the postmitotic neurons for proper synapse patterning. In contrast, unc-37 is required in both developing and postmitotic neurons. The synaptic tiling defects of unc-4 mutants are suppressed by bar-1/β-catenin mutation, which positively regulates the expression of ceh-12/HB9. Ectopic ceh-12 expression partly underlies the synaptic tiling defects of unc-4 and unc-37 mutants. Our results reveal a novel postmitotic role of neuronal cell fate determinants in synapse pattern formation through inhibiting the canonical Wnt signaling pathway.
