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
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.
