Laboratory of Cell Recognition and Pattern Formation, Graduate School of Biostudies, South Campus Research Building (Building G), Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Genes Cells. 2010 May;15(5):485-500. doi: 10.1111/j.1365-2443.2010.01399.x. Epub 2010 Apr 7.
Diverse neuronal subtypes develop distinctive morphologies of dendritic arbors that receive synaptic or sensory inputs. Dendritic arbors of many subtypes take on a polarized shape, and one underlying mechanism is unidirectionally biased elongation of dendritic branches. As reported herein, we found that Drosophila Crossveinless-c (Cv-c) was a key regulator for such directional growth. In the cv-c mutant, two subclass of multidendritic sensory neurons examined formed dorsally directed branches; however, dendritic branches had difficulty in growing along the anterior-posterior (A-P) body axis. Cv-c belongs to the family of Rho GTPase-activating proteins (RhoGAPs) and is the homolog of human tumor suppressor DLC1. The RhoGAP activity of Cv-c was required cell-autonomously for the A-P-oriented growth, and Cv-c elevated the GTPase activity of Rho1 and Cdc42 in a cell-free assay. Our analysis of genetic interactions suggested that Rho1 was the target of Cv-c in vivo. All of our results suggest that Cv-c contributes to sprouting and subsequent growth of the A-P-oriented branches through negative regulation of Rho1. We discuss a role of Cv-c in dendritic growth in response to environmental cues.
不同的神经元亚型会发育出具有接收突触或感觉输入的独特树突分支形态。许多亚型的树突分支呈极化形状,其潜在的机制之一是树突分支的单向偏侧伸长。本文报道称,我们发现果蝇 Crossveinless-c(Cv-c)是这种定向生长的关键调节因子。在 cv-c 突变体中,两种多树突感觉神经元亚类形成了背向分支;然而,树突分支难以沿前后(A-P)体轴生长。Cv-c 属于 Rho GTPase 激活蛋白(RhoGAP)家族,是人类肿瘤抑制因子 DLC1 的同源物。Cv-c 的 RhoGAP 活性对于 A-P 定向生长是细胞自主必需的,并且 Cv-c 在细胞游离测定中提高了 Rho1 和 Cdc42 的 GTPase 活性。我们对遗传相互作用的分析表明,Rho1 是 Cv-c 在体内的靶标。我们所有的结果表明,Cv-c 通过负向调节 Rho1 来促进 A-P 定向分支的发芽和随后的生长。我们讨论了 Cv-c 在响应环境线索时对树突生长的作用。