The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration.
Spinal cord oligodendrocytes originate in the ventricular zone and subsequently migrate to white matter, stop, proliferate, and differentiate. Here we demonstrate a role for the chemokine CXCL1 and its receptor CXCR2 in patterning the developing spinal cord. Signaling through CXCR2, CXCL1 inhibited oligodendrocyte precursor migration. The migrational arrest was rapid, reversible, concentration dependent, and reflected enhanced cell/substrate interactions. White matter expression of CXCL1 was temporo-spatially regulated. Developing CXCR2 null spinal cords contained reduced oligodendrocytes, abnormally concentrated at the periphery. In slice preparations, CXCL1 inhibited embryonic oligodendrocyte precursor migration, and widespread dispersal of postnatal precursors occurred in the absence of CXCR2 signaling. These data suggest that population of presumptive white matter by oligodendrocyte precursors is dependent on localized expression of CXCL1.
Tsai
Hui-Hsin
HH
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Frost
Emma
E
To
Vivien
V
Robinson
Shenandoah
S
Ffrench-Constant
Charles
C
Geertman
Robert
R
Ransohoff
Richard M
RM
Miller
Robert H
RH
D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D023063:Receptors, Interleukin-8B