Parcellation of the striatal complex into dorsal and ventral districts
| Autor: | Sylvia M. Evans, Fu Chin Liu, Hsin-An Ko, Sunny Li-Yun Chang, Janice Hsin-Jou Hao, Shih-Yun Chen, Ting-Hao Huang, Kuan-Ming Lu, Yu-Ting Yan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Mice Transgenic Nerve Tissue Proteins Striatum Nucleus accumbens Biology Basal Ganglia Nucleus Accumbens Mice 03 medical and health sciences 0302 clinical medicine Interneurons Basal ganglia medicine Animals Enhancer Transcription factor Homeodomain Proteins Neurons Multidisciplinary Olfactory tubercle Ventral striatum Intracellular Signaling Peptides and Proteins Cell Differentiation Biological Sciences Phenotype Corpus Striatum Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Ventral Striatum Female Neuroscience 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1921007117 |
| Popis: | 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 two-tier 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. |
| Databáze: | OpenAIRE |
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