Transcription Factor 4 Safeguards Hippocampal Dentate Gyrus Development by Regulating Neural Progenitor Migration
| Autor: | Zhengang Yang, Di Yun, Yunli Xie, Thomas Behnisch, Yuqun Cai, Chunyang Wang, Tianxiang Tang, Yafei Wang, Zhiheng Lu, Fang Fang, Zheping Cai, Yandong Zhang, Yilan Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Cognitive Neuroscience Mice Transgenic Hippocampal formation Biology 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Transcription Factor 4 Neural Stem Cells Cell Movement Pregnancy Animals Progenitor cell Transcription factor 030304 developmental biology Progenitor 0303 health sciences Effector Dentate gyrus TCF4 Neuroepithelial cell Mice Inbred C57BL Dentate Gyrus Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cerebral cortex (New York, N.Y. : 1991). 30(5) |
| ISSN: | 1460-2199 |
| Popis: | The dentate gyrus (DG) of the hippocampal formation plays essential roles in learning and memory. Defective DG development is associated with neurological disorders. Here, we show that transcription factor 4 (Tcf4) is essential for DG development. Tcf4 expression is elevated in neural progenitors of the dentate neuroepithelium in the developing mouse brain. We demonstrate that conditional disruption of Tcf4 in the dentate neuroepithelium leads to abnormal neural progenitor migration guided by disorganized radial glial fibers, which further leads to hypoplasia in the DG. Moreover, we reveal that Wnt7b is a key downstream effector of Tcf4 in regulating neural progenitor migration. Behavioral analysis shows that disruption of integrity of the DG impairs the social memory highlighting the importance of proper development of the DG. These results reveal a critical role for Tcf4 in regulating DG development. As mutations in TCF4 cause Pitt–Hopkins syndrome (PTHS) characterized by severe intellectual disability, our data also potentially provide insights into the basis of neurological defects linked to TCF4 mutations. |
| Databáze: | OpenAIRE |
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