细胞类型特异的神经元树突分支形成是神经环路形成的基础。然而，树突形态建成的分子机制还未被完全阐明。秀丽线虫PVD神经元特异地在背区和腹区的皮肤-体壁肌肉之间形成大量树突分支。我们的前期工作发现，敲除eat-17导致PVD神经元在侧区异常地形成大量树突分支，而在背区和腹区的分支数目严重减少。敲除raby3或膜泡运输调控基因rab-6.2或lin-10导致类似的侧区异常分支增多表型。eat-17敲低导致皮肤表达的SAX-7蛋白水平下降。因此，我们提出以下假设：EAT-17和RABY3通过调控促树突分支因子SAX-7的运输和定位而调控树突形态建成。本研究将结合遗传学、活体显微成像和生物化学等多种手段，研究EAT-17和RABY3调控树突形态建成的分子机制。本项目的研究成果将会帮助我们更好地理解树突发育的分子机制，并为开发神经环路功能性重建以治疗神经退化等疾病提供理论支撑。

Formation of cell-type specific dendritic arbors is critical for neural circuit assembly. However, the molecular mechanisms underlying dendrite morphogenesis are still poorly understood. C. elegans PVD neurons specifically develop exuberant dendritic branches sandwiched by the skin and body wall muscles in the dorsal and ventral regions. Our unpublished results revealed that loss of eat-17 caused ectopic branch formation in the lateral region, while the number of branches in the dorsal and ventral regions was severely decreased. Similar ectopic branch formation defect was observed in the lateral region of knock-out mutants of raby3 and vesicular trafficking gene rab-6.2 or lin-10. Knock-down of eat-17 decreased the expression of SAX-7 in the skin cells. Thus, we hypothesize that EAT-17 and RABY3 regulate dendrite morphogenesis via trafficking/localizing the dendritic branching cue SAX-7. We plan to study how EAT-17 and RABY3 regulate dendrite morphogenesis by using assays including worm genetics, live cell imaging and biochemistry. This study will give us a better understanding on the molecular basis of dendrite development, and help us functionally re-build neural circuits to cure disorders such as neurodegeneration.