title: Endothelin-1 regulates oligodendrocyte development.
abstract: In the postnatal brain, oligodendrocyte progenitor cells (OPCs) arise from the subventricular zone (SVZ) and migrate into the developing white matter, where they differentiate into oligodendrocytes and myelinate axons. The mechanisms regulating OPC migration and differentiation are not fully defined. The present study demonstrates that endothelin-1 (ET-1) is an astrocyte-derived signal that regulates OPC migration and differentiation. OPCs in vivo and in culture express functional ET(A) and ET(B) receptors, which mediate ET-1-induced ERK (extracellular signal-regulated kinase) and CREB (cAMP response element-binding protein) phosphorylation. ET-1 exerts both chemotactic and chemokinetic effects on OPCs to enhance cell migration; it also prevents lineage progression from the O4(+) to the O1(+) stage without affecting cell proliferation. Astrocyte-conditioned medium stimulates OPC migration in culture through ET receptor activation, whereas multiphoton time-lapse imaging shows that selective ET receptor antagonists or anti-ET-1 antibodies inhibit OPC migration from the SVZ. Inhibition of ET receptor activity also derepresses OPC differentiation in the corpus callosum in slice cultures. Our findings indicate that ET-1 is a soluble astrocyte-derived signal that regulates OPC migration and differentiation during development.
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Gadea
authors.forename: Adan
authors.initials: A
authors.lastname: Aguirre
authors.forename: Tarik F
authors.initials: TF
authors.lastname: Haydar
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gallo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001323:Autoantibodies; D001921:Brain / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D017077:Culture Media, Conditioned; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000502:physiology*; D051381:Rats; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D013552:Swine
chemical_list: D001323:Autoantibodies; D017077:Culture Media, Conditioned; D017362:Cyclic AMP Response Element-Binding Protein; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D048049:Extracellular Signal-Regulated MAP Kinases
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