Usp11 controls cortical neurogenesis and neuronal migration through Sox11 stabilization
Open Access
- 12 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (7), eabc6093
- https://doi.org/10.1126/sciadv.abc6093
Abstract
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.Funding Information
- Ministry of Science and Technology, Taiwan (108-2639-B-001-001-ASP)
This publication has 42 references indexed in Scilit:
- Cis-regulatory control of corticospinal system development and evolutionNature, 2012
- SoxC Transcription Factors Are Required for Neuronal Differentiation in Adult Hippocampal NeurogenesisJournal of Neuroscience, 2012
- Sequentially acting Sox transcription factors in neural lineage developmentGenes & Development, 2011
- Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cellsNature, 2011
- Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitorsNature Communications, 2010
- The N-Myc-DLL3 Cascade Is Suppressed by the Ubiquitin Ligase Huwe1 to Inhibit Proliferation and Promote Neurogenesis in the Developing BrainDevelopmental Cell, 2009
- Trim11 modulates the function of neurogenic transcription factor Pax6 through ubiquitin–proteosome systemGenes & Development, 2008
- Mind Bomb 1-Expressing Intermediate Progenitors Generate Notch Signaling to Maintain Radial Glial CellsNeuron, 2008
- The establishment of neuronal properties is controlled by Sox4 and Sox11Genes & Development, 2006
- Ubiquitin C-terminal hydrolase L1 regulates the morphology of neural progenitor cells and modulates their differentiationJournal of Cell Science, 2006