Dendritic morphology is inextricably linked to neuronal function. Systematic large-scale screens combined with genetic mapping have uncovered several mechanisms underlying dendrite morphogenesis. However, a comprehensive overview of participating molecular mechanisms is still lacking. Here, we conducted an efficient clonal screen using a collection of mapped P-element insertions that were previously shown to cause lethality and eye defects in Drosophila melanogaster. Of 280 mutants, 52 exhibited dendritic defects. Further database analyses, complementation tests, and RNA interference validations verified 40 P-element insertion genes as being responsible for the dendritic defects. Twenty-eight mutants presented severe arbor reduction, and the remainder displayed other abnormalities. The intrinsic regulators encoded by the identified genes participate in multiple conserved mechanisms and pathways, including the protein folding machinery and the chaperonin-containing TCP-1 (CCT) complex that facilitates tubulin folding. Mutant neurons in which expression of CCT4 or CCT5 was depleted exhibited severely retarded dendrite growth. We show that CCT localizes in dendrites and is required for dendritic microtubule organization and tubulin stability, suggesting that CCT-mediated tubulin folding occurs locally within dendrites. Our study also reveals novel mechanisms underlying dendrite morphogenesis. For example, we show that Drosophila Nogo signaling is required for dendrite development and that Mummy and Wech also regulate dendrite morphogenesis, potentially via Dpp- and integrin-independent pathways. Our methodology represents an efficient strategy for identifying intrinsic dendrite regulators, and provides insights into the plethora of molecular mechanisms underlying dendrite morphogenesis.

树突形态与神经元功能密不可分。系统的大规模筛选与遗传作图相结合，揭示了树突形态发生的几种机制。但是，仍然缺乏对参与的分子机制的全面概述。在这里，我们使用了一系列映射的P元素插入物进行了有效的克隆筛选，这些插入物先前显示会导致致死性和眼缺陷。果蝇。在280个突变体中，有52个表现出树突状缺陷。进一步的数据库分析，互补测试和RNA干扰验证验证了40个P元素插入基因是导致树突状缺陷的原因。28个突变体表现出严重的乔木减少，其余的表现出其他异常。由已识别基因编码的内在调节子参与多种保守的机制和途径，包括蛋白质折叠机制和促进微管蛋白折叠的含伴侣蛋白的TCP-1（CCT）复合物。CCT4或CCT5的表达被耗尽的突变神经元表现出严重阻碍了树突的生长。我们显示，CCT位于树突中，是树突微管组织和微管蛋白稳定性所必需的，提示CCT介导的微管蛋白折叠在树突内局部发生。我们的研究还揭示了树突形态发生的新机制。例如，我们表明果蝇Nogo信号对于树突的发育是必需的，并且Mummy和Wech也可能通过Dpp和整联蛋白非依赖性途径调节树突的形态发生。我们的方法论代表了一种识别固有枝晶调节剂的有效策略，并提供了深入了解枝晶形态发生基础的众多分子机制的见解。