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生物通官微
陪你抓住生命科技
跳动的脉搏
生物通官微
陪你抓住生命科技
跳动的脉搏
郑毅教授《PNAS》文章验证神经祖细胞假说
【字体： 大 中 小 】 时间：2006年10月24日 来源：生物通
编辑推荐：
在最新一期（10月20日）的Cell杂志上，由辛辛那提儿童医院医学中心的华裔教授郑毅（Yi Zheng）与毕业于国立台湾大学的Chia-Yi kuan助理教授领导的研究组公布了他们有关神经元祖细胞研究的最新发现。
生物通报道：在最新一期（10月20日）的Cell杂志上，由辛辛那提儿童医院医学中心的华裔教授郑毅（Yi Zheng）与毕业于国立台湾大学的Chia-Yi kuan助理教授领导的研究组公布了他们有关神经元祖细胞研究的最新发现。
哺乳动物大脑的NE（telencephalic neuroepithelium，端脑神经上皮）具有一种顶-基底极性(apical-basal polarity)，其特点是神经祖细胞和adherens交叉点定位在apical/ventricular表面，并且向上的放射状glia/progenitor纤维向着pial/basal表面。NE在发育过程中需要扩展、分化成大脑半球。
决定这种NE顶－基底极性的信号途径目前还没有完全了解。研究人员推测Rho家族GTP酶Cdc42可能起到一个关键作用，因为这种蛋白控制着许多物质中以cadherin为基础的细胞间接合与细胞极性过程。
在这项新的研究中，郑教授的实验室通过使用Foxgl-Cre系来敲除小鼠胚胎中端脑神经祖细胞中的Cdc42的基因靶向技术来验证这个假说。
他们发现Cdc42的敲除消除了NE中PAR6、aPKC、E-cadherin、β－catenin和Numb蛋白在顶部定位的趋向性，并且严重损害了nestin阳性放射性纤维的延伸。
因此，神经祖细胞分散在整个NE中，并且Cdc-42缺陷端脑无法发育分成两个大脑半球。但是，Sonic hedgehog和dorso-ventral的中线表达模式不受Cdc-42敲除的硬性。
这些研究结果表明Cdc42在大脑NE形成顶－基底极性中起到关键作用，从而证实了之前提出的假说。（生物通杨遥）
附郑毅实验室介绍等资料：
The research activities of Dr. Yi Zheng's laboratory focus on studies of the function and mechanism of regulation of the Rho family small GTP-binding proteins of Ras superfamily. The Rho GTPases are a class of intracellular signal transducers that play important roles in the regulation of diverse cellular activities including actin cytoskeleton reorganization, transcription activation, and DNA synthesis. Like Ras, mutation, overexpression or disruption of the normal mode of regulation of these GTP-binding and GTP-hydrolyzing molecular switches may lead to cellular transformation, morphological changes, and developmental disorders. By using a variety of current cellular, molecular, biochemical, and mouse genetic approaches, Dr. Zheng's lab attempts to understand the molecular mechanisms of signal transduction processes involving Rho GTPases, their regulators, and effector targets. The ultimate goals are to develop novel therapeutic reagents that may interfere with specific Rho pathways related to human pathological conditions.
The ongoing research projects include:
§ Functional characterizations of the Dbl-family guanine nucleotide exchange factors (GEFs) of Rho GTPases. The goals are to understand the structure-function relationships of the conserved DH, PH, and other functional domains of the guanine nucelotide exchange factors, to dissect the upstream signaling pathways leading to the activation of specific Rho GTPases through the Dbl family GEFs, and to implicate the GEFs in tumorigenesis process using a mouse model system.
§ Functional and mechanistic studies of the Rho GTPase-activating proteins (GAPs). The goals are to understand the functional interactions between the RhoGAP domains and Rho proteins and to determine the cellular functions and mode of regulation of these putative downregulators or effectors of Rho GTPases.
§ Investigation of the functional interaction between Rho GTPases and p53 tumor suppressor pathway. The goals are to dissect the molecular pathways of Rho GTPases that cooperate with p53 deficiency in promoting cell transformation and invasion and to implicate individual members of the Rho family as anti-cancer targets in a mouse model.
§ Development of small molecule inhibitors and other strategies that interfere with specific Rho protein functions. The goal is that the selected compounds could be explored as novel therapeutic reagents acting on specific Rho GTPase mediated signaling pathways that are associated with human diseases.
§ Development of animal model systems by using transgenic and gene targeting methods in mice to study the physiological roles of Rho GTPases and their regulators. We are specifically focusing on the generation and/or characterization of RhoA, Cdc42 and Rac1 conditional knockout mice and the Cdc42GAP knockout mice.
Chia-Yi Kuan, MD, PhD
Assistant Professor
Assistant Professor of Pediatrics
513-636-0245
513-636-4317
M.D.: National Taiwan University, Taiwan, 1989.
