4月22日國際神經(jīng)科學(xué)雜志《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）發(fā)表了中科院神經(jīng)所周嘉偉研究員所領(lǐng)導(dǎo)科研團(tuán)隊(duì)的研究成果——“調(diào)節(jié)中腦多巴胺能神經(jīng)元發(fā)育的基因”。這一成果提出了這類神經(jīng)元胚胎發(fā)育的模式,，為進(jìn)一步認(rèn)識基底神經(jīng)節(jié)的發(fā)育過程提供了新的資料,。
中腦多巴胺能（mDA）神經(jīng)元在人類和動(dòng)物的運(yùn)動(dòng)能力、情緒調(diào)節(jié)等重要生理過程中發(fā)揮著極其關(guān)鍵的作用,，這些細(xì)胞功能和結(jié)構(gòu)的異常與多種神經(jīng)精神疾病如帕金森病,、藥物成癮和精神分裂癥等有著非常密切的關(guān)系,。已知這類疾病的發(fā)生與某些在mDA神經(jīng)元發(fā)育過程中起重要作用的基因有關(guān)，了解mDA神經(jīng)元的發(fā)育過程將有助于理解這些疾病的發(fā)生和發(fā)展,，但迄今為止有關(guān)這類神經(jīng)元發(fā)育的分子機(jī)制還知之甚少,。
印敏（中科院生化細(xì)胞所）、劉蜀西和尹延青等建立了mDA神經(jīng)元分化過程中全基因表達(dá)譜及差異變化基因的數(shù)據(jù)庫,，鑒定到一批在mDA神經(jīng)元中特異表達(dá)的基因,，提出了mDA神經(jīng)元發(fā)育可以分為四個(gè)性質(zhì)各異的時(shí)空階段。有意思的是,，他們還發(fā)現(xiàn)在轉(zhuǎn)錄因子Ebf1基因敲除小鼠,，黑質(zhì)（DA神經(jīng)元集中區(qū)域之一）無法正常形成,，并導(dǎo)致黑質(zhì)紋狀體投射通路發(fā)育不全,。進(jìn)一步研究發(fā)現(xiàn)，Ebf1通過控制mDA神經(jīng)元向黑質(zhì)致密帶的遷移而調(diào)節(jié)黑質(zhì)在胚胎期的形成,。因此,，Ebf1是第一個(gè)被發(fā)現(xiàn)的控制黑質(zhì)DA神經(jīng)元遷移的基因，這對認(rèn)識發(fā)育時(shí)期多巴胺能神經(jīng)元富集的不同神經(jīng)核團(tuán)之間（如腹側(cè)被蓋區(qū)與黑質(zhì)）如何相互分離的問題提供了重要線索,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
