Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
| Autor: | Ruey-Hwa Chen, Shang Yin Chiang, Shen Ju Chou, Hung-Chih Kuo, Hsin Chieh Wu, Hsin Yi Chen, Chia Fang Wang, Nai Hsing Yeh, Shu-Yu Lin, Yi-Shuian Huang, Jou Ho Shih |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Neurogenesis
Biology Cell fate determination medicine.disease_cause SOXC Transcription Factors 03 medical and health sciences Mice 0302 clinical medicine Neurodevelopmental disorder Developmental Neuroscience Cell Movement Cortex (anatomy) medicine Animals Research Articles 030304 developmental biology Cerebral Cortex Neurons 0303 health sciences Mutation Multidisciplinary SciAdv r-articles Cell Differentiation medicine.disease medicine.anatomical_structure Cerebral cortex Neuron Protein stabilization Neuroscience 030217 neurology & neurosurgery Research Article Signal Transduction |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Protein deubiquitination contributes to cortical development, and its dysregulation is linked to intellectual disability. The role of protein stabilization in cortical development remains poorly understood. A recessive mutation in the USP11 gene is found in a rare neurodevelopmental disorder with intellectual disability, but its pathogenicity and molecular mechanism are unknown. Here, we show that mouse Usp11 is expressed highly in embryonic cerebral cortex, and Usp11 deficiency impairs layer 6 neuron production, delays late-born neuronal migration, and disturbs cognition and anxiety behaviors. Mechanistically, these functions are mediated by a previously unidentified Usp11 substrate, Sox11. Usp11 ablation compromises Sox11 protein accumulation in the developing cortex, despite the induction of Sox11 mRNA. The disease-associated Usp11 mutant fails to stabilize Sox11 and is unable to support cortical neurogenesis and neuronal migration. Our findings define a critical function of Usp11 in cortical development and highlight the importance of orchestrating protein stabilization mechanisms into transcription regulatory programs for a robust induction of cell fate determinants during early brain development. |
| Databáze: | OpenAIRE |
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