DYF-4在神经元树突和纤毛发育过程中的功能研究

The outgrowth of axons and dendrites from neuronal cell bodies to their appropriate targets requires precise and orderly guidance. Recent study discovered a new mode termed “retrograde extension”: neuronal processes are made by anchoring dendrite tips at their target locations while the cell body pulls away. However, the molecular mechanism of this mode is poorly understood. In our study, we found that when glia cell expressed gene dyf-4 was mutated, amphid and phasmid sensory neuron dendrite tips couldn’t be anchored, and kept moving with the migrating cell bodies. Study the function of DYF-4 in dendrite development will help us to further understand the molecular mechanism of “retrograde extension”. . Cilia are sensory organelles emanating from the cell surface of most eukaryotic cells. Cilia development disorders cause a wide spectrum of human diseases termed ciliopathies. In Caenorhabditis elegans, cilia are at the tips of sensory neuron dendrites. We found that dyf-4 also regulated the cilia development. In dyf-4 mutants, the cilia length is much shorter than the wild type. How DYF-4, an extra ciliary protein, regulates cilia development is also of our interest.

神经元突起从细胞体到达预定的靶位点需要精细的调控。近年来，人们在秀丽隐杆线虫（Caenorhabditis elegans）感觉神经元中发现了一种新的突出生长模式，即逆行延伸（retrograde extension）：神经元树突顶端固定不动，细胞体往后移动至特定位置。迄今为止，逆行延伸的分子调控机制还鲜有报道。我们的研究发现dyf-4突变后，线虫头部和尾部感觉神经元树突的顶端无法固定，树突显著缩短至细胞体附近。进一步研究发现dyf-4在神经胶质细胞中表达。研究胶质细胞来源的DYF-4如何调控树突顶端的固定将有利于我们更好地理解这一新型的延伸机制。. 纤毛是突出于细胞表面、由微管组成的毛发状细胞器，其发育缺陷会导致多种人类疾病。线虫中，纤毛位于感觉神经元树突的顶端。我们发现dyf-4突变体中纤毛的发育也受到明显影响。纤毛外蛋白如何影响纤毛的发育也是我们研究的重点之一。

神经元树突延伸与周围神经胶质细胞发育的协调对于神经元功能至关重要，但其潜在的分子机制仍知之甚少。通过秀丽隐杆线虫的全基因组诱变筛选，我们坚定到dyf-4和daf-6两个突变体，它们均在神经元树突延伸方面具有缺陷。 DAF-6编码神经胶质特异的膜蛋白，在胶质细胞形态发生中起重要作用。我们的研究发现DYF-4编码神经胶质分泌的细胞外蛋白。进一步的研究表明，DYF-4与DAF-6相互作用，并与DAF-6共定位于神经胶质通道，且和DAF-6通过相同的途径调控神经胶质通道的形成。此外，我们证明了已报道的daf-6抑制剂同样可以抑制dyf-4突变体中感觉神经元树突延伸缺陷和纤毛发生缺陷的表型。总体而言，我们的数据表明，DYF-4可能充当修补相关受体DAF-6的新型配体/调节剂，从而促进神经胶质通道的正确形成，并间接影响神经突的延伸和纤毛生成。