Growth factors and transcription factors in oligodendrocyte development

• Published in: Journal of Cell Science Vol. 1991; no. Supplement_15; pp. 117 - 123
• Main Authors: COLLARINI, E. J, PRINGLE, N, MUDHAR, H, STEVENS, G, KUHN, R, MONUKI, E. S, LEMKE, G, RICHARDSON, W. D
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Cambridge Company of Biologists 01-02-1991
• Subjects: Biological and medical sciences; Cell physiology; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Responses to growth factors, tumor promotors, other factors; Cell proliferation; Oligodendrocyte; Platelet derived growth factor
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.1991.supplement_15.16

O-2A progenitor cells, the precursors of oligodendrocytes in the central nervous system (CNS), probably originate in the subventricular germinal zones of the developing CNS, and subsequently migrate away from there to populate the rest of the CNS with oligodendrocytes. We are trying to understand how the O-2A progenitor cells interact with their changing environment as they migrate, and how this influences each stage of their development into mature, myelinating oligodendrocytes. In this article we summarize evidence that platelet-derived growth factor (PDGF) is important for stimulating O-2A progenitor cell proliferation in vivo, and describe our efforts to map the distribution of PDGF and its receptors in the developing rat CNS by in situ hybridization and immunohistochemistry. These studies suggest that, in the CNS, PDGF a-receptor subunits may be restricted to O-2A lineage cells that have started to migrate away from the subventricular zones towards their final destinations. Many neurons express the A and/or B chains of PDGF, and astrocytes express the A chain, but it is not yet clear which of these cell types might be the major source of PDGF for O-2A lineage cells in vivo. O-2A progenitor cells can be purified and maintained in a proliferating state in vitro by culturing in the presence of PDGF and bFGF. Under these conditions, the POU transcription factor SCIP/Tst-1 is expressed at a high level; when oligodendrocyte differentiation is initiated by withdrawing the growth factors, SCIP/Tst-1 mRNA is rapidly down-regulated, followed by a decline in SCIP/Tst-1 protein and sequential activation of myelin-specific genes. These observations suggest that SCIP/Tst-1 may be mechanistically involved in the transition from proliferation to differentiation in the 0-2A lineage. By in situ hybridization, SCIP/Tst-1 appears also to be expressed in developing neurons, so perhaps it fulfils a similar function in several different cell lineages in the CNS.