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Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization

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 expres...

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Autores principales: Chiang, Shang-Yin, Wu, Hsin-Chieh, Lin, Shu-Yu, Chen, Hsin-Yi, Wang, Chia-Fang, Yeh, Nai-Hsing, Shih, Jou-Ho, Huang, Yi-Shuian, Kuo, Hung-Chih, Chou, Shen-Ju, Chen, Ruey-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880594/
https://www.ncbi.nlm.nih.gov/pubmed/33579706
http://dx.doi.org/10.1126/sciadv.abc6093
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author Chiang, Shang-Yin
Wu, Hsin-Chieh
Lin, Shu-Yu
Chen, Hsin-Yi
Wang, Chia-Fang
Yeh, Nai-Hsing
Shih, Jou-Ho
Huang, Yi-Shuian
Kuo, Hung-Chih
Chou, Shen-Ju
Chen, Ruey-Hwa
author_facet Chiang, Shang-Yin
Wu, Hsin-Chieh
Lin, Shu-Yu
Chen, Hsin-Yi
Wang, Chia-Fang
Yeh, Nai-Hsing
Shih, Jou-Ho
Huang, Yi-Shuian
Kuo, Hung-Chih
Chou, Shen-Ju
Chen, Ruey-Hwa
author_sort Chiang, Shang-Yin
collection PubMed
description 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.
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spelling pubmed-78805942021-02-22 Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization Chiang, Shang-Yin Wu, Hsin-Chieh Lin, Shu-Yu Chen, Hsin-Yi Wang, Chia-Fang Yeh, Nai-Hsing Shih, Jou-Ho Huang, Yi-Shuian Kuo, Hung-Chih Chou, Shen-Ju Chen, Ruey-Hwa Sci Adv Research Articles 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. American Association for the Advancement of Science 2021-02-12 /pmc/articles/PMC7880594/ /pubmed/33579706 http://dx.doi.org/10.1126/sciadv.abc6093 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Chiang, Shang-Yin
Wu, Hsin-Chieh
Lin, Shu-Yu
Chen, Hsin-Yi
Wang, Chia-Fang
Yeh, Nai-Hsing
Shih, Jou-Ho
Huang, Yi-Shuian
Kuo, Hung-Chih
Chou, Shen-Ju
Chen, Ruey-Hwa
Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
title Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
title_full Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
title_fullStr Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
title_full_unstemmed Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
title_short Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
title_sort usp11 controls cortical neurogenesis and neuronal migration through sox11 stabilization
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880594/
https://www.ncbi.nlm.nih.gov/pubmed/33579706
http://dx.doi.org/10.1126/sciadv.abc6093
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