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Title: Platelet derived growth factor and its receptors in the developing rat central nervous system
Author: Pringle, Nigel Patrick
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1992
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In the mature rat optic nerve there are several types of postmitotic glial cells including oligodendrocytes and type-1 astrocytes. Type-1 astrocytes develop from one type of precursor cell, while oligodendrocytes develop from a different progenitor cell known as an O-2A progenitor. O-2A progenitor cells can be stimulated to divide in vitro by mitogens secreted by cultured cortical (type-1-like) astrocytes or by purified platelet-derived growth factor (PDGF). By northern blotting I show that cultured cortical astrocytes synthesize the A chain of PDGF. Its time course of appearance in the brain and its distribution in the optic nerve suggest that type-1 astrocytes might be a source of PDGF-A in vivo, and that PDGF-A is probably important for O-2A progenitor proliferation during development. O-2A progenitors express the α-subunit of the PDGF receptor PDGF-αR. To visualize these cells and other cells in the CNS that might express PDGF-αR, I performed in situ hybridization using a probe specific to PDGF-αR. During late embryonic and early postnatal neurogenesis, the spatiotemporal distribution of PDGF-αR+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-αR may be expressed preferentially by cells of the O-2A lineage and might, therefore, be a useful marker for studying the development of this lineage from its earliest origins in the ventricular zones of the developing brain and spinal cord. By in situ hybridization I showed that, in the E14 spinal cord, PDGF-αR is expressed in the basal ventricular zone in two longitudinal columns, one each side of the central canal. These columns are initially comprised of only two cells in the cross-sectional plane, but the PDGF-αR cells appear subsequently to multiply and disseminate throughout the spinal cord. In the brain, PDGF-αR+ cells seem to arise in a specialized germinal zone beneath the foramen of Monro, in the ventral half of the developing diencephalon. These results lead me to propose that the earliest oligodendrocyte precursors are generated in very restricted regions of the ventricular zones of the developing brain and spinal cord during a brief window of time around E14.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available