Parcellation of the striatal complex into dorsal and ventral districts

Shih Yun Chen, Kuan Ming Lu, Hsin An Ko, Ting Hao Huang, Janice Hsin Jou Hao, Yu Ting Yan, Sunny Li Yun Chang, Sylvia M. Evans, Fu Chin Liu*

*此作品的通信作者

研究成果: Article同行評審

13 引文 斯高帕斯(Scopus)

摘要

The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington's disease, Parkinson's disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2- indirect pathways. We show that Nolz-1, through the I12b enhancer, represses Dlx1/2, allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of Nolz-1 and Dlx1/2 can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the twotier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.

原文English
頁(從 - 到)7418-7429
頁數12
期刊Proceedings of the National Academy of Sciences of the United States of America
117
發行號13
DOIs
出版狀態Published - 31 3月 2020

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