4月22日国际神经科学杂志《神经科学杂志》(Journal of Neuroscience)发表了中科院神经所周嘉伟研究员所领导科研团队的研究成果——“调节中脑多巴胺能神经元发育的基因”。这一成果提出了这类神经元胚胎发育的模式,为进一步认识基底神经节的发育过程提供了新的资料。
中脑多巴胺能(mDA)神经元在人类和动物的运动能力、情绪调节等重要生理过程中发挥着极其关键的作用,这些细胞功能和结构的异常与多种神经精神疾病如帕金森病、药物成瘾和精神分裂症等有着非常密切的关系。已知这类疾病的发生与某些在mDA神经元发育过程中起重要作用的基因有关,了解mDA神经元的发育过程将有助于理解这些疾病的发生和发展,但迄今为止有关这类神经元发育的分子机制还知之甚少。
印敏(中科院生化细胞所)、刘蜀西和尹延青等建立了mDA神经元分化过程中全基因表达谱及差异变化基因的数据库,鉴定到一批在mDA神经元中特异表达的基因,提出了mDA神经元发育可以分为四个性质各异的时空阶段。有意思的是,他们还发现在转录因子Ebf1基因敲除小鼠,黑质(DA神经元集中区域之一)无法正常形成,并导致黑质纹状体投射通路发育不全。进一步研究发现,Ebf1通过控制mDA神经元向黑质致密带的迁移而调节黑质在胚胎期的形成。因此,Ebf1是第一个被发现的控制黑质DA神经元迁移的基因,这对认识发育时期多巴胺能神经元富集的不同神经核团之间(如腹侧被盖区与黑质)如何相互分离的问题提供了重要线索。(生物谷Bioon.com)
生物谷推荐原始出处:
The Journal of Neuroscience, April 22, 2009, 29(16):5170-5182; doi:10.1523/JNEUROSCI.5569-08.2009
Ventral Mesencephalon-Enriched Genes That Regulate the Development of Dopaminergic Neurons In Vivo
Min Yin,1,2 * Shuxi Liu,2 * Yanqing Yin,2 Sen Li,2 Zhihua Li,1 Xuefei Wu,1 Bo Zhang,2 Siew-Lan Ang,3 Yuqiang Ding,2 and Jiawei Zhou2
1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, and 2State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and 3Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom
Mesodiencephalic dopaminergic (mDA) neurons are critical for movement control and other physiological activities. However, the molecular mechanisms underlying their development are poorly understood. We aimed to establish the expression profiles of genes involved in this process and unravel genetic programs that control late development of mDA neurons. We compared genome-wide gene expression profiles of developing mouse ventral mesencephalon (VM) using microarrays. We identified a set of genes that show spatially and temporally restricted expression in the VM in an Ngn2 (neurogenin 2)-dependent manner and are potentially important for mDA neuron development. Functional analysis on mice lacking the VM-specific gene early B-cell factor 1 (Ebf1) revealed that Ebf1 is essential for the terminal migration of mDA neurons in the substantia nigra pars compacta. Thus, we identified a set of VM-enriched genes that are important for mDA neuron development. Our analysis also provides a genetic framework for further investigation of the molecular mechanisms mediating mDA neuron development.