| Abstract No.: | B-B2034 |
| Country: | Canada |
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| Title: | PATTERNS OF EXPRESSION OF OLIGODENDROCYTE SPECIFIC PROTEINS DURING DEVELOPMENT OF THE MOUSE BRAIN |
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| Authors/Affiliations: | 1 Zhicheng Zhou*; 3 Joumana Mustapha; 2 Emma E Frost;
1 Department of Pathology, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, MB, Canada; 2 Dept.s Pathology; Human Anatomy and Cell Science; Biochemistry and Medical Genetics, Winnipeg, MB, Canada; 3 Manitoba Institute of Child Health, University of Manitoba, Winnipeg, MB, Canada
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| Content: | Objective: To map the expression patterns of platelet derived growth factor-A (PDGF-A), and its receptor PDGF Receptor-alpha (PDGFR alpha), during development of the embryonic mouse brain. INTRODUCTION: Oligodendrocytes (OL) produce myelin, which is essential for normal conductance of nerve impulses throughout the CNS. OL originate in the germinal matrix (GM) of the developing CNS. A variety of factors regulate the OL progenitor cells (OPs) in the developing CNS, such as extracellular matrix (ECM) proteins, soluble factors and axonal cues1-3. As the brain develops, OPs migrate away from the GM to populate white matter tracts such as the corpus callosum. OPs migrate and proliferate in response to growth factors, including platelet-derived growth factor A (PDGF-A), and fibroblast growth factor-2 (FGF2)4. PDGF-A is essential for the development of myelin in the brain5, and its receptor, PDGFR alpha is commonly used as a marker of OP6.
Materials and methods: We collected and sectioned brains of embryonic mice from days 11.5 to 20.5. Dissected heads were fixed in 10% buffered formalin for 36 hours at 4ºC. Tissue was then cryopreserved in 30% sucrose prior to embedding in OCT cryocompound, and stored at -80ºC until sectioned. Brains were sectioned at 12mm from olfactory bulb to brain stem. Serial sections were stored at -80ºC until stained. Immunohistochemical analysis of PDGF-A and PDGFR alpha was performed as previously described7. RESULTS: We show that PDGFR alpha (a marker of OPs) immunoreactivity is seen only in the GM at the earliest stage of brain development studied (E11.5). As the brain develops, PDGFR alpha immunoreactivity is seen at increasingly larger distances from the GM. Whereas PDGF-A can be seen consistently everywhere from E11.5 to E19.5.
Conclusion: PDGF-A is known to be a potent mitogen for OP and an important regulator of OP migration. Early hypotheses suggested a chemotactic gradient of growth factors such as PDGF. However, our findings do not support such a gradient. Indeed, PDGF-A immunoreactivity is seen throughout the developing mouse brain, whereas PDGFR alpha immunoreactivity is restricted to the putative location of the migrating OPs. This work was funded by The Dr. Paul H.T. Thorlakson Foundation Fund and the Manitoba Institute of Child Health.
(1) Frost, E.et al. Dev Neurosci 1996, 18, 266-73.
(2) Hardy, R.et al. J Neurosci Res 1993, 36, 121-6.
(3) Barres, B. A.et al. J. Cell Biol. 1999, 147, 1123-1128.
(4) Armstrong, R.et al. Ann N Y Acad Sci 1991, 633, 520-2.
(5) Fruttiger, M.et al. Development 1999, 126, 457-67.
(6) Armstrong, R. C. Methods 1998, 16, 282-92.
(7) Frost, E. E.et al. J Neurobiol 2003, 54, 457-72.
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