No abstract

Pleiotrophin (PTN) is a heparin-binding, 18 kDa secretory protein that functions to induce mitogenesis, angiogenesis, differentiation, and transformation in vitro. PTN gene (Ptn) expression is highly regulated during development and is highest at sites in which mitogenesis, angiogenesis, and differentiation are active. In striking contrast, with the exception of the neuron, the Ptn gene is only minimally expressed in adults. We now demonstrate that Ptn gene expression is strikingly upregulated within 3 d in OX42-positive macrophages, astrocytes, and endothelial cells in areas of developing neovasculature after focal cerebral ischemia in adult rat. Ptn gene expression remains upregulated in these same cells and sites 7 and 14 d after ischemic injury. However, expression of the Ptn gene is significantly decreased in cortical neurons 6 and 24 hr after injury and is undetectable in degenerating neurons at day 3. Neurons in contralateral cortex continue to express Ptn in levels equal to control, uninjured brain. It is suggested that PTN may have a vital role in neovascular formation in postischemic brain and that postischemic brain is an important model in which to analyze sequential gene expression in developing neovasculature. In contrast, Ptn gene expression in injured neurons destined not to recover is strikingly reduced, and potentially its absence may contribute to the failure of the neuron to survive.

We recently reported that the platelet-derived growth factor (PDGF) A-chain gene is highly exp e in neurons of embryonic and adult mouse central nervous system and suggested that its secretion by neurons may support development and maintenance of gla. We have now analysed the levels and sites of expression of the cognate PDGF a-receptor gene in brain and spinal cord ofembryonic and adult mice by in situ hybridization. The predominant cell populations in both gray and white matter expressing rpts of the PDGF a-receptor gene are glal cells or their precursors. T pts c isntly were not detected in neurons. Expressd of the PDGF a-receptor gene was first observed at embryonic day 15, increased through posatal day 14, and fell to lower levels in adults. Expression of the a-receptor gene corresponds in temporal sequence to the developmental period of glal miration and prolfferation and to the expression of PDGF A by neurons.The results indicate that glia but not neurons have the potentia to respond to PDGF A and suggest that neurons inflnence glal cel development throug paracrine gulation. and E18 and postnatal day 1 (P1), P7, P14, P28, and P56 were prepared as described (5).A mouse cDNA [corresponding to residues 2198-2582 of the PDGF a receptor (9) (3)(4)(5). We recently demonstrated that the platelet-derived growth factor (PDGF) A-chain gene is expressed in high levels in neuronal populations of embryonic and adult mice (5). The time course of appearance of A-chain gene transcripts and their near ubiquitous expression in neurons suggested that the neuron may be the major source of the PDGF A-chain in the nervous system and that the neuron may function in a previously undescribed role in the paracrine regulation of central nervous system (CNS) development. Earlier work had indicated that PDGF functions to regulate glial differentiation in vitro (6, 7). However, it was not appreciated that the neuron expressed high levels of the PDGF A-chain gene. To understand the significance of these findings, we analyzed the cellular localization and time course of expression of the gene encoding the cognate receptor for PDGF A, the PDGF a receptor (8, 9), within the CNS ofembryonic and postnatal mice by in situ hybridization to seek these cells that coordinately express the a-receptors.MATERIALS AND METHODS Tissue sections including cerebral cortex, hippocampus, midbrain, thalamus, pons, cerebellum, and spinal cord from BALB/c/B1O mice at embryonic day 8 (E8), E10, E12, E15, RESULTS Specifically labeled and control sections from E8, E10, E12, E15, and E18 embryos and from P1, P7, P14, P28, and P56 animals were analyzed by both darkfield and brightfield microscopy. Transcripts of the PDGF a-receptor gene were not seen in the CNS of E8, E10, or E12 embryos, whereas transcripts were readily detected in both spinal cord and brain by darkflield microscopy of E15 embryos. The 35S-hybridization signal was particularly intense in developing white matter (Fig. 1 A-C, arrows) and found in clusters around the nuclei of small cells. T...