Fig. 1: Mutation of the homeodomain transcription factor dve-1 disrupts the removal of postsynaptic sites in GABAergic motor neurons.

a Top, schematic of C. elegans indicating DD GABAergic motor neurons (purple). Bottom, schematic depicting motor circuit before (left) and after (right) remodeling. DD motor neurons (purple), cholinergic motor neurons (blue). b Top, timeline of remodeling, approximate timing of transitions between larval stages and adulthood are indicated. Bars indicate the duration of DD synaptic remodeling for wild-type (gray) and dve-1 mutants (purple). Elimination of dorsal cord iAChR clusters is completed by 22 h after hatch for wild-type whereas dorsal iAChR clusters persist through adulthood in dve-1 mutants. Middle, quantification of iAChR remodeling in DD neurons of wild-type (left) and dve-1 mutants (right). X-axis time from hatch in hours. Animals are binned according to the distribution of iAChR puncta as dorsal only (white), ventral only (black), or dorsal and ventral (gray). Bottom, representative images of dorsal and ventral ACR-12::GFP (iAChRs, green) clusters for wild-type (left) and dve-1 mutants (right) at the times indicated. Two-tailed Fischer’s exact test with Bonferroni correction. Scale bar, 5 µm. c Domain structure of DVE-1. SATB-like domains and homeodomains (HD) are indicated. Site of substitution produced by uf171 missense mutation (red) and region of tm4803 deletion mutation (blue) and insertion (red) are indicated. Box, predicted protein structure (AlphaFold) and sequence alignment for HD1 (NCBI Conserved Domains). d Fluorescent confocal images of synaptic iAChR clusters in GABAergic DD processes of the dorsal nerve cord at L4 stage. GABA rescue refers to specific expression of wild-type dve-1 cDNA using the unc-47 promoter. In this and subsequent figures, iAChR refers to ACR-12::GFP unless otherwise indicated. Images on each line are from different animals. Scale, 5 µm. e Quantification of the number of iAChR clusters per 25 µm of the L4 stage dorsal nerve cord for the genotypes indicated. Each dot represents a single animal and n for each genotype is indicated by numbers in parentheses. Bars indicate mean ± SEM. ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, one-way ANOVA with Tukey’s multiple comparisons test.