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中枢神经系统胚胎脑室区中层粘连蛋白和整合素的模式。

Patterns of laminins and integrins in the embryonic ventricular zone of the CNS.

作者信息

Lathia Justin D, Patton Bruce, Eckley D Mark, Magnus Tim, Mughal Mohamed R, Sasaki Takako, Caldwell Maeve A, Rao Mahendra S, Mattson Mark P, ffrench-Constant Charles

机构信息

Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.

出版信息

J Comp Neurol. 2007 Dec 20;505(6):630-43. doi: 10.1002/cne.21520.

Abstract

The extracellular matrix (ECM) provides both a physical framework and a microenvironment that supplies instructive signals from the earliest stages of multicellular development. As a first step toward understanding the role of the ECM in regulating the behavior of neural stem cells (NSCs), here we show the localization of laminins, a heterotrimeric family of ECM molecules expressed in many different stem cell microenvironments, and their corresponding receptors in the embryonic murine ventricular zone (VZ) within which the NSCs undergo symmetrical and asymmetrical divisions required for cortical development. In addition to the presence of laminins containing both the alpha2 and alpha4 chains, we find distinct patterns of ECM receptor expression in the VZ and in the overlying cortex. Neural stem cells derived from the VZ express high levels of the integrin laminin receptor alpha6beta1. At developmental stages at which NSCs undergo asymmetrical divisions, integrin beta1 was unevenly distributed in some mitotic pairs at the ventricular wall. These results suggest a significant role in the regulation of NSC fate for laminin/integrin signaling within the microenvironment of the VZ and provide a framework for future molecular and cellular analyses of the role of the ECM in neural development.

摘要

细胞外基质(ECM)提供了一个物理框架和一个微环境,从多细胞发育的最早阶段起就提供指导性信号。作为理解ECM在调节神经干细胞(NSC)行为中作用的第一步,我们在此展示层粘连蛋白的定位,层粘连蛋白是在许多不同干细胞微环境中表达的细胞外基质分子的异源三聚体家族,以及它们在胚胎小鼠脑室区(VZ)中的相应受体,神经干细胞在该区域进行皮层发育所需的对称和不对称分裂。除了存在含有α2和α4链的层粘连蛋白外,我们还在VZ和上层皮层中发现了细胞外基质受体表达的不同模式。源自VZ的神经干细胞表达高水平的整合素层粘连蛋白受体α6β1。在神经干细胞进行不对称分裂的发育阶段,整合素β1在脑室壁的一些有丝分裂对中分布不均。这些结果表明,层粘连蛋白/整合素信号在VZ微环境中对神经干细胞命运的调节中起重要作用,并为未来对细胞外基质在神经发育中作用的分子和细胞分析提供了框架。

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