ESCRT-I protein UBAP1 controls ventricular expansion and cortical neurogenesis via modulating adherens junctions of radial glial cells

Danping Lu; Yiqiang Zhi; Huizhen Su; Xiang Lin; Jingjing Lin; Yan Shi; Wenxiang Yi; Chaoyin Hong; Tongtong Zhang; Zhifei Fu; Li-Yu Chen; Zhiqi Zhao; Rong Li; Zhiheng Xu; Wanjin Chen; Ning Wang; Dan Xu

Cell Reports (Mar 2024)

ESCRT-I protein UBAP1 controls ventricular expansion and cortical neurogenesis via modulating adherens junctions of radial glial cells

Danping Lu,
Yiqiang Zhi,
Huizhen Su,
Xiang Lin,
Jingjing Lin,
Yan Shi,
Wenxiang Yi,
Chaoyin Hong,
Tongtong Zhang,
Zhifei Fu,
Li-Yu Chen,
Zhiqi Zhao,
Rong Li,
Zhiheng Xu,
Wanjin Chen,
Ning Wang,
Dan Xu

Affiliations

Danping Lu: Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou 350004, China; College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
Yiqiang Zhi: Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou 350004, China; School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
Huizhen Su: Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China
Xiang Lin: Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China
Jingjing Lin: Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China
Yan Shi: Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou 350004, China
Wenxiang Yi: School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
Chaoyin Hong: Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China
Tongtong Zhang: School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
Zhifei Fu: Public Technology Service Center, Fujian Medical University, Fuzhou 350122, China
Li-Yu Chen: College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
Zhiqi Zhao: State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Rong Li: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
Zhiheng Xu: State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Wanjin Chen: Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China; Corresponding author
Ning Wang: Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China; Corresponding author
Dan Xu: Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou 350004, China; Corresponding author

Journal volume & issue: Vol. 43, no. 3
p. 113818

Abstract

Read online

Summary: Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and β-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords