Dyf-4 Regulates Patched-Related/Daf-6-Mediated Sensory Compartment Formation In C. Elegans

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 protein. Further investigations revealed that DYF-4 interacts with DAF-6 and functions in a same pathway as DAF-6 to regulate sensory compartment formation. Furthermore, we demonstrated that reported glial suppressors of daf-6 could also restore dendrite elongation and ciliogenesis in both dyf-4 and daf-6 mutants. Collectively, our data reveal that DYF-4 is a regulator for DAF-6 which promotes the proper formation of the glial channel and indirectly affects neurite extension and ciliogenesis.Author summary In C. elegans sensory organ, the ciliated neuronal endings are wrapped in a luminal channel formed by glial cells, forming a specialized sensory compartment critical for sensory activity. Coordination of glial channel formation, dendritic tip anchoring and ciliogenesis are critical for the formation of a functional sensory compartment. DAF-6, a patched-related glial membrane protein, was reported to play an important role in glial channel morphogenesis, but the molecular function and regulatory mechanism of DAF-6 remain poorly understood. Here, we found that DYF-4, a glia-secreted protein, interacts and colocalizes with DAF-6, and functions in a same pathway as DAF-6 to regulate sensory compartment formation. We propose that DYF-4 is a novel regulator for DAF-6 to control sensory compartment formation.