title: Slit2 regulates the dispersal of oligodendrocyte precursor cells via Fyn/RhoA signaling.
abstract: Oligodendrocyte precursor cells (OPCs) are a unique type of glia that are responsible for the myelination of the central nervous system. OPC migration is important for myelin formation during central nervous system development and repair. However, the precise extracellular and intracellular mechanisms that regulate OPC migration remain elusive. Slits were reported to regulate neurodevelopmental processes such as migration, adhesion, axon guidance, and elongation through binding to roundabout receptors (Robos). However, the potential roles of Slits/Robos in oligodendrocytes remain unknown. In this study, Slit2 was found to be involved in regulating the dispersal of OPCs through the association between Robo1 and Fyn. Initially, we examined the expression of Robos in OPCs both in vitro and in vivo. Subsequently, the Boyden chamber assay showed that Slit2 could inhibit OPC migration. RoboN, a specific inhibitor of Robos, could significantly attenuate this effect. The effects were confirmed through the explant migration assay. Furthermore, treating OPCs with Slit2 protein deactivated Fyn and increased the level of activated RhoA-GTP. Finally, Fyn was found to form complexes with Robo1, but this association was decreased after Slit2 stimulation. Thus, we demonstrate for the first time that Slit2 regulates the dispersal of oligodendrocyte precursor cells through Fyn and RhoA signaling.
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jiazhen
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Su
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: chenghe@smmu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D051076:Proto-Oncogene Proteins c-fyn; D011971:Receptors, Immunologic; D020742:rhoA GTP-Binding Protein; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C494961:Fyn protein, rat