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The Journal of Neuroscience, December 1, 2004, 24(48):10888-10899; doi:10.1523/JNEUROSCI.3302-04.2004

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Development/Plasticity/Repair
Isolation of a Novel Platelet-Derived Growth Factor-Responsive Precursor from the Embryonic Ventral Forebrain

Andrew Chojnacki and Samuel Weiss

Genes and Development Research Group, Department of Cell Biology and Anatomy, University of Calgary, Faculty of Medicine, Calgary, Alberta, T2N 4N1 Canada

Oligodendrocyte progenitor cells express platelet-derived growth factor (PDGF) receptor- 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.

Key words: oligodendrocyte; precursor; PDGF; forebrain; Olig; BMP

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Received Aug 11, 2004; revised October 15, 2004; accepted October 20, 2004.

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