Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development

Yixun Su; Xiaorui Wang; Yujian Yang; Liang Chen; Wenlong Xia; Kimberly K Hoi; Hui Li; Qi Wang; Guangdan Yu; Xiaoying Chen; Shouyu Wang; Yuxin Wang; Lan Xiao; Alexei Verkhratsky; Stephen P J Fancy; Chenju Yi; Jianqin Niu

doi:10.1016/j.neuron.2022.10.032

Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development

Neuron. 2023 Jan 18;111(2):190-201.e8. doi: 10.1016/j.neuron.2022.10.032. Epub 2022 Nov 15.

Authors

Yixun Su¹, Xiaorui Wang², Yujian Yang³, Liang Chen⁴, Wenlong Xia⁵, Kimberly K Hoi⁵, Hui Li¹, Qi Wang¹, Guangdan Yu², Xiaoying Chen², Shouyu Wang², Yuxin Wang², Lan Xiao², Alexei Verkhratsky⁶, Stephen P J Fancy⁷, Chenju Yi⁸, Jianqin Niu⁹

Affiliations

¹ Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing 400038, China; Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China.
² Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing 400038, China.
³ Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing 400038, China; Department of Ophthalmology, Army Specialty Medical Center, Third Military Medical University, Chongqing 400042, China.
⁴ Department of Orthopedics, Army Specialty Medical Center, Third Military Medical University, Chongqing 400042, China.
⁵ Department of Neurology, Department of Pediatrics, Division of Neuroimmunology and Glial Biology, Newborn Brain Research Institute, University of California at San Francisco, San Francisco, CA 94158, USA.
⁶ Faculty of Biology, Medicine and Health, University of Manchester, Manchester M139PL, UK; Achucarro Center for Neuroscience, IKERBASQUE, Bilbao 48011, Spain.
⁷ Department of Neurology, Department of Pediatrics, Division of Neuroimmunology and Glial Biology, Newborn Brain Research Institute, University of California at San Francisco, San Francisco, CA 94158, USA. Electronic address: stephen.fancy@ucsf.edu.
⁸ Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China. Electronic address: yichj@mail.sysu.edu.cn.
⁹ Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University, Chongqing 400038, China. Electronic address: jianqinniu@tmmu.edu.cn.

Abstract

Oligodendrocyte precursor cells (OPCs) undergo an extensive and coordinated migration in the developing CNS, using the pre-formed scaffold of developed blood vessels as their physical substrate for migration. While OPC association with vasculature is critical for dispersal, equally important for permitting differentiation and proper myelination of target axons is their appropriate and timely detachment, but regulation of this process remains unclear. Here we demonstrate a correlation between the developmental formation of astrocytic endfeet on vessels and the termination of OPC perivascular migration. Ex vivo and in vivo live imaging shows that astrocyte endfeet physically displace OPCs from vasculature, and genetic abrogation of endfoot formation hinders both OPC detachment from vessels and subsequent differentiation. Astrocyte-derived semaphorins 3a and 6a act to repel OPCs from blood vessels at the cessation of their perivascular migration and, in so doing, permit subsequent OPC differentiation by insulating them from a maturation inhibitory endothelial niche.

Keywords: astrocyte endfoot; myelination; oligodendrocyte precursor cells; perivascular migration; semaphorins.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Astrocytes
Cell Differentiation / physiology
Cell Movement / physiology
Oligodendrocyte Precursor Cells*
Oligodendroglia / physiology

Abstract

Publication types

MeSH terms

Grants and funding