The role of bone morphogenetic protein 7 in cortical neurogenesis

Title: The role of bone morphogenetic protein 7 in cortical neurogenesis
Authors: Chitty, David W
Date: 2011
Abstract: The cortex is formed through a series of well-organized processes by which neural progenitor cells proliferate, commit to different cell fates and differentiate to neuronal and glial cell types. These complex processes are regulated by a wide range of intrinsic and extrinsic factors, which include members of the bone morphogenetic protein (BMP) family and their receptors. Accumulating evidence suggests that BMP7, a factor clinically used to repair bone fracture and kidney failure, is involved in brain development by contributing to both neural induction and cell differentiation. In this study, the role of BMP7 in cortical neurogenesis was examined during embryonic development in mice. Specifically, neuronal differentiation was enhanced in cortical cultures following treatment with low concentration recombinant human BMP7, whereas higher concentrations enhanced glial differentiation. Comparative analysis of BMP receptor expression during cortical development indicated that activin receptor type IIB (ActRIIB) expression is significantly higher than other BMP receptors during neurogenesis, whereas it is significantly down-regulated following the onset of gliogenesis. Furthermore, the neutralization of ActRIIB in cortical cultures reduced levels of neuronal differentiation, suggesting its involvement in BMP7-induced cortical neurogenesis. Lastly, to further the study of BMP7, its signaling pathway and the downstream nuclear targets, lentiviral systems were developed and optimized to allow BMP7 overexpression and ActRIIB knockdown in the cortex. Similar to the commercially available recombinant BMP7, cortical neurogenesis was enhanced in the presence of lentiviral-derived BMP7.
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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