Developmental Expression of Platelet-Derived Growth Factor α-Receptor in Neurons and Glial Cells of the Mouse CNS

Abstract

The synthesis of platelet-derived growth factor-α receptor (PDGF-αR) is commonly attributed to oligodendrocyte progenitors during late embryonic and postnatal development. However, we recently demonstrated that mature neurons could also synthesize PDGF-αR, emphasizing a larger role for this receptor than previously described. In the present study, to analyze the pattern of PDGF-αR expression during postnatal development of the mouse CNS, we usedin situhybridization and immunohistochemistry on brain and spinal cord tissue sections. We found that, in addition to immature cells of the oligodendrocyte lineage, neurons of various CNS regions express PDGF-αR transcripts and protein as early as postnatal day 1 (P1). Whereas neuronal expression was maintained at all ages, the oligodendroglial expression strongly decreased after P21. In the adult, PDGF-αR was detected in very few oligodendrocyte progenitors scattered in the cerebral cortex or in white matter tracts, thus suggesting the presence of PDGF-αR on O-2Aadultprogenitors. In the mature CNS, PDGF-αR transcripts and protein were mainly localized in neurons of numerous structures, such as the olfactory bulb, cerebral cortex, hippocampus, and brainstem nuclei and in motor neurons of the ventral horn of the spinal cord. The differential expression of PDGF-αR in oligodendroglia and neurons argues in favor of several roles of PDGF during development.

Cell-Surface Glycoprotein of Oligodendrocyte Progenitors Involved in Migration

“…The ganglioside GD3 is expressed by oligodendrocyte progenitor cells but is not exclusive to these cells (Cammer and Zhang, 1996). In P6 forebrain, we observed AN2-positive cells that expressed the PDGF ␣-receptor, an accepted marker for oligodendroglial progenitor cells (Pringle et al, 1992;Pringle and Richardson, 1993;Hall et al, 1996), but expression of this receptor may also extend to other cell types (Oumesmar et al, 1997). Oligodendrocyte progenitorcells may be heterogeneous in their antigenic profile (Spassky et al, 1998): the definition of further markers for these cells will help clarify this.…”

The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice

“…Remarkably, the expression of the two major Shc isoforms (ShcA p46 and ShcA p52 ) is also restricted to these proliferative VZ and SVZ (Conti et al, 1997;Cattaneo and Pelicci, 1998), both in embryonic and postnatal brain, supporting the hypothesis that the Shc isoform controls the neural stem cell proliferation. In adult brain, the adult precursor cells in the SVZa also express a set of growth factor receptors such as plateletderived growth factor (PDGF)-K-receptor, epidermal growth factor (EGF) receptor and tyrosine kinase receptor, TrkB (Seroogy et al, 1995;Snyder et al, 1996;Oumesmar et al, 1997). Since phosphatidylinositol 5-phosphatases of the SHIP family may inhibit Ras/ MAPK activation and regulate the e¡ect of PI 3-K activity by their ability to dephosphorylate PtdIns(3,4,5)P 3 (Vanhaesebroeck and Water¢eld, 1999), they therefore appear to be able to regulate the growth factor signaling cascades.…”

Malignant glioma: genetics and biology of a grave matter

“…Conversely, neuron-specific enolasedirected overexpression of PDGF-AA results in a marked increase in the number of glial progenitors that, upon differentiation, generate an excess of abnormally localized oligodendrocytes that subsequently undergo apoptosis before birth (Calver et al 1998). In the adult brain, PDGF-R-␣ expression is restricted to the ventricular and subventricular zone of the lateral ventricles, possibly restricted to neural stem cells, whereas PDGF is widely expressed by neurons and astrocytes (Oumesmar et al 1997). In the subventricular zone of the lateral ventricle, PDGF-R-␣, in addition to other proposed molecules (Gates et al 1995), may play a role in the normal differentiation and migration of neural stem cells into neurons as they migrate to the olfactory bulb (Louis 1994).…”