Transcription factor 4 controls positioning of cortical projection neurons through regulation of cell adhesion
| Autor: | Zheping Cai, Guanglei Hu, Yilan Zhang, Lei Xiao, Saiyong Chen, Na Li, Lanhui Zeng, Yu Gu, Yandong Zhang, Yunli Xie, Tianxiang Tang, Songhui Hu, Yafei Wang, Qiong Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Biology 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Transcription Factor 4 Intellectual Disability Biological neural network Extracellular Cell Adhesion Humans Hyperventilation Cell adhesion Molecular Biology Transcription factor Neurons Cell adhesion molecule Facies TCF4 Cortex (botany) Psychiatry and Mental health Electrophysiology 030104 developmental biology nervous system Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular psychiatry. 26(11) |
| ISSN: | 1476-5578 |
| Popis: | The establishment of neural circuits depends on precise neuronal positioning in the cortex, which occurs via a tightly coordinated process of neuronal differentiation, migration, and terminal localization. Deficits in this process have been implicated in several psychiatric disorders. Here, we show that the transcription factor Tcf4 controls neuronal positioning during brain development. Tcf4-deficient neurons become mispositioned in clusters when their migration to the cortical plate is complete. We reveal that Tcf4 regulates the expression of cell adhesion molecules to control neuronal positioning. Furthermore, through in vivo extracellular electrophysiology, we show that neuronal functions are disrupted after the loss of Tcf4. TCF4 mutations are strongly associated with schizophrenia and cause Pitt-Hopkins syndrome, which is characterized by severe intellectual disability. Thus, our results not only reveal the importance of neuronal positioning in brain development but also provide new insights into the potential mechanisms underlying neurological defects linked to TCF4 mutations. |
| Databáze: | OpenAIRE |
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