Development of an Adult CNS Stem Cell Marking System

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Neurogenesis continues in adult brain in discrete regions including the hippocampus and the subventricular zone. The exact functional significance of neurogenesis in adult hippocampus is still being debated. However altered hippocampal neurogenesis may play a pathophysiological role in a number of neuropsychiatric disorders. Presently progenitor cells in adult brain are most commonly identified by bromodeoxyuridine (BrdU) labeling and their fate followed with specific differentiation markers. However this methodology suffers several limitations including issues of sensitivity and permanence. Here we propose to use a green fluorescent protein (GFP) based transgenic system that utilizes the Cre recombinase site specific DNA recombination system and the lac repressor inducible/regulatable system to develop an efficient method for permanently marking nestin lineage CNS stem cells in adult brain. This system will allow the fate of nestin lineage stem cells to be followed indefinitely in adult brain irrespective of their differentiation along neuronal or non-neuronal lines.