Gu Wen-Li, Fu Sai-Li, Wang Yan-Xia, Li Ying, Lü He-Zuo, Xu Xiao-Ming, Lu Pei-Hua
Department of Neurobiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
BMC Neurosci. 2009 Oct 21;10:128. doi: 10.1186/1471-2202-10-128.
Neural precursor cells (NPCs) are defined by their ability to proliferate, self-renew, and retain the potential to differentiate into neurons and glia. Deciphering the factors that regulate their behaviors will greatly aid in their use as potential therapeutic agents or targets. Chondroitin sulfate proteoglycans (CSPGs) are prominent components of the extracellular matrix (ECM) in the central nervous system (CNS) and are assumed to play important roles in controlling neuronal differentiation and development.
In the present study, we demonstrated that CSPGs were constitutively expressed on the NPCs isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to abolish the function of endogenous CSPGs on NPCs, it induced a series of biological responses including the proliferation, differentiation and migration of NPCs, indicating that CSPGs may play a critical role in NPC development and differentiation. Finally, we provided evidence suggesting that integrin signaling pathway may be involved in the effects of CSPGs on NPCs.
The present study investigating the influence and mechanisms of CSPGs on the differentiation and migration of NPCs should help us to understand the basic biology of NPCs during CNS development and provide new insights into developing new strategies for the treatment of the neurological disorders in the CNS.
神经前体细胞(NPCs)的定义是其具有增殖、自我更新以及保留分化为神经元和神经胶质细胞的潜能。解读调控其行为的因素将极大地有助于将其用作潜在的治疗剂或靶点。硫酸软骨素蛋白聚糖(CSPGs)是中枢神经系统(CNS)细胞外基质(ECM)的重要组成部分,被认为在控制神经元分化和发育中发挥重要作用。
在本研究中,我们证明CSPGs在从E16大鼠胚胎脑分离的NPCs上组成性表达。当使用软骨素酶ABC消除内源性CSPGs对NPCs的功能时,它诱导了一系列生物学反应,包括NPCs的增殖、分化和迁移,表明CSPGs可能在NPCs的发育和分化中起关键作用。最后,我们提供的证据表明整合素信号通路可能参与CSPGs对NPCs的影响。
本研究调查CSPGs对NPCs分化和迁移的影响及机制,应有助于我们了解中枢神经系统发育过程中NPCs的基本生物学特性,并为开发治疗中枢神经系统神经疾病的新策略提供新见解。