Event
Bioengineering Seminar Series: Vittorio Gallo
Wednesday, October 17, 2007
11:00 a.m.
2108 Chemical and Nuclear Engineering Building
Professor J. Helim Aranda-Espinoza
(301) 405-8250
helim@umd.edu
Gliogenesis and Glial Regeneration in the Developing and Injured Brain
Presented by Vittorio Gallo
Children's National Medical Center
Glial cells, including astrocytes and oligodendrocytes, represent approximately 90% of the cells in the mature mammalian brain. Oligodendrocytes generate myelin in the central nervous system, and axonal myelination is an essential function for proper propagation of action potentials. Gliogenesis largely occurs in the postnatal brain after neurons have matured and the majority of synaptic connections have been established. The subventricular zone (SVZ) is a major neurogenic and gliogenic region of the postnatal brain. In this region, cell divisions continue to take place throughout life, as complex bidirectional interactions between intrinsic molecular programs and extrinsic determinants induce neural stem cells and progenitors to proliferate, migrate and differentiate, and undergo apoptotic cell death. Significant progress has been recently made in the identification of extracellular factors that regulate neural progenitor proliferation, migration and differentiation in the SVZ. However, several lines of evidence also indicate that these functions are intrinsically controlled by a molecular network of kinases and accessory proteins.
In my presentation, I will discuss the role of intrinsic and extrinsic regulators of neural progenitor cell development and gliogenesis in the postnatal brain. In particular, I will focus on the function of the cell cycle regulator Cdk2, and of the EGFR and its ligands. Our findings reveal that Cdk2, although functionally redundant in perinatal SVZ, assumes critical importance for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4 expression and activity. Using a gain- and loss-of-function approach, we also found that overexpression of human EGFR accelerates oligodendrogenesis and developmental myelination through the expansion of a glial progenitor population in the SVZ. Importantly, EGFR overexpression also promotes remyelination and functional recovery under pathological conditions, i.e. following focal demyelination of mouse corpus callosum.
Our findings support the notion that both intrinsic as well as extrinsic regulators of neural progenitor cell development control gliogenesis and glial repair in the postnatal brain. The elucidation of critical molecular cues that control proliferation, migration and differentiation of endogenous neural progenitor cells may open new avenues for the development of neuronal and glial replacement therapies for neurodegenerative diseases and other central nervous system injuries that require manipulation of endogenous progenitors or transplantation of exogenous cells.
