Isolation of a novel platelet-derived growth factor-responsive precursor from the embryonic ventral forebrain.
Oligodendrocyte progenitor cells express platelet-derived growth factor (PDGF) receptor-alpha and, when expanded in PDGF only, have been shown to generate oligodendrocytes and astrocytes but never neurons. Recent evidence suggests that oligodendrocytes are generated by a common progenitor that also generates neurons but not astrocytes. We used the neurosphere culture system to isolate embryonic ventral forebrain, PDGF-responsive precursors (PRPs). We report that the medial ganglionic eminence is the source of PRP-generated neurospheres and that the progeny can differentiate into parvalbumin-positive interneurons, oligodendrocytes, and astrocytes. Thyroid hormone and bone morphogenetic protein-2 (BMP-2) promote the mutually exclusive differentiation of oligodendrocytes and neurons, respectively, whereas ciliary neurotrophic factor acts with BMP-2 to suppress OLIG2 expression and promote astroglial differentiation. PRPs require fibroblast growth factor-2 together with PDGF to maintain self-renewal, which is dependent on sonic hedgehog signaling. We present evidence for forebrain oligodendrocytes and parvalbumin-positive interneurons being generated by a common precursor and elucidate signals regulating the multiple differentiation routes of the progeny of this precursor.
Chojnacki
Andrew
A
Genes and Development Research Group, Department of Cell Biology and Anatomy, University of Calgary, Faculty of Medicine, Calgary, Alberta, T2N 4N1 Canada.
Weiss
Samuel
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D053823:Hedgehog Proteins; D007395:Interneurons / Q000166:cytology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology; D010320:Parvalbumins / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology; D013234:Stem Cells / Q000145:classification / Q000166:cytology* / Q000187:drug effects; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D015415:Biomarkers; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020934:Ciliary Neurotrophic Factor; D053823:Hedgehog Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D010982:Platelet-Derived Growth Factor; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; D014284:Triiodothyronine; D016222:Fibroblast Growth Factor 2