CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
PLoS Genet. 2021 Jun 11;17(6):e1009618. doi: 10.1371/journal.pgen.1009618. eCollection 2021 Jun.
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.
神经突与周围神经胶质发育的协调对神经元功能至关重要，但其中的分子机制仍知之甚少。通过在秀丽隐杆线虫中的全基因组诱变筛选，我们发现 dyf-4 和 daf-6 是两个在树突延伸方面具有相似缺陷的突变体。DAF-6 编码一种胶质特异性 patched 相关膜蛋白，在神经胶质形态发生中发挥重要作用。我们克隆了 dyf-4，并发现 DYF-4 编码一种胶质分泌蛋白。进一步的研究表明，DYF-4 与 DAF-6 相互作用，并与 DAF-6 发挥相同的作用途径，以调节感觉区室的形成。此外，我们还证明，报道的 daf-6 胶质抑制因子也可以恢复 dyf-4 和 daf-6 突变体中树突伸长和纤毛发生。总之，我们的数据表明 DYF-4 是 DAF-6 的调节剂，它促进了神经胶质通道的正确形成，并间接地影响了神经突延伸和纤毛发生。
