POSTNATAL NEURONAL PRECURSORS AND BRAIN REPAIR

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DESCRIPTION: The subventricular zone (SVZ) in juvenile and adult mammalian brains, including primates, contain a population of rapidly proliferative cells. New neurons and glia can be derived from these proliferating SVZ precursors in adult mice. Adult SVZ cells can also be grown in vitro with EGF or bFGF and these cells retain the potential to form neurons and glia in vitro. In rodents, SVZ cells migrate several mm to the olfactory bulb where they differentiate into neurons. These SVZ cells migrate associated with each other, forming chains of neuronal precursors (chain migration), faithfully reaching the olfactory bulb without raidal glia or axons for guidance. An extensive network for chain migration exits in the SVZ of adult mice suggesting that an unprecedented traffic of neuronal precursors exist in the adult mammalian brain. The goal is to determine the potential of the adult SVZ to generate new neurons for brain repair. To this end, the following question will be addressed. 1) Is the olfactory bulb required for the migration and proliferation of SVZ precursors? 2) Can SVZ precursors generate new neurons after transplantation into different regions of the adult brain? 3) Do chains of neuronal precursors exist in the brain of other adult vertebrates including primates and humans? 4) Which of the 5 cell types that the investigator has recently characterized in the SVZ of adult mice grow with EGF or bFGF in vitro? 5) Can SVZ precursors, either isolated directly from the brain or cultured in vitro with growth factors integrate and generate different neuronal types following transfer into the embryonic brain?