An extracellular protein regulates patched-related/DAF-6-mediated sensory compartment formation in C. elegans

Abstract Coordination of neurite extension with surrounding glia development is critical for neuronal function, but the underlying molecular mechanisms remain poorly understood. Through a genome-wide mutagenesis screen in C. elegans , we identified dyf-4 and daf-6 as two mutants sharing similar defects in dendrite extension. DAF-6 encodes a glia-specific patched-related membrane protein that plays vital roles in glial morphogenesis. We cloned dyf-4 and found that DYF-4 encodes a glia-secreted extracellular protein. Intriguingly, DYF-4 colocalizes with DAF-6 along the glial channel. Further investigations revealed that DYF-4 directly interacts with DAF-6 and regulates its proper membrane localization. Notably, reported glial suppressors of daf-6 could also restore dendrite elongation and ciliogenesis in both dyf-4 and daf-6 mutants. Collectively, our data suggest that secreted DYF-4 likely acts as a novel ligand/regulator for the patched-related receptor DAF-6 which promotes the proper formation of the glial channel and indirectly affects neurite extension and ciliogenesis.