title: CXCR7 Mediates Neural Progenitor Cells Migration to CXCL12 Independent of CXCR4.
abstract: Neural progenitor cell (NPC) migration is an essential process for brain development, adult neurogenesis, and neuroregeneration after brain injury. Stromal cell-derived factor-1 (SDF-1, CXCL12) and its traditional receptor CXCR4 are well known to regulate NPC migration. However, the discovery of CXCR7, a newly identified CXCL12 receptor, adds to the dynamics of the existing CXCL12/CXCR4 pair. Antagonists for either CXCR4 or CXCR7 blocked CXCL12-mediated NPC migration in a transwell chemotaxis assay, suggesting that both receptors are required for CXCL12 action. We derived NPC cultures from Cxcr4 knockout (KO) mice and used transwell and stripe assays to determine the cell migration. NPCs derived from Cxcr4 KO mice polarized and migrated in response to CXCL12 gradient, suggesting that CXCR7 could serve as an independent migration receptor. Furthermore, Cxcr4 KO NPCs transplanted into the adult mouse striatum migrated in response to the adjacent injection of CXCL12, an effect that was blocked by a CXCR7 antagonist, suggesting that CXCR7 also mediates NPC migration in vivo. Molecular mechanism studies revealed that CXCR7 interact with Rac1 in the leading edge of the polarized NPCs in the absence of CXCR4. Both CXCR7 and Rac1 are required for extracellular signal-regulated kinases (ERK) 1/2 activation and subsequent NPC migration, indicating that CXCR7 could serve as a functional receptor in CXCL12-mediated NPC migration independent of CXCR4. Together these results reveal an essential role of CXCR7 for CXCL12-mediated NPC migration that will be important to understand neurogenesis during development and in adulthood.
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.|Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.|Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Yuju
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.|Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Song
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.|Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.|Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.|Department of Pharmacology and Experimental Neuroscience and, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Jialin C
authors.initials: JC
authors.lastname: Zheng
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; C515256:Cxcl12 protein, mouse; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D048052:Mitogen-Activated Protein Kinase 3; D020830:rac1 GTP-Binding Protein
keywords: Cell migration; Cell signaling; Chemokine receptor; Neural stem cell
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