Identification and regulation of neural stem cells in the adult mammalian hypothalamus

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Adult mammalian neural stem cells (NSCs) provide striking evidence of plasticity of the central nervous system and open up a new possibility for cell replacement therapy for neurological disorders. No solid evidence has been demonstrated for the existence of NSCs in the adult hypothalamus, which is an essential region for many important behaviors that are essential for survival. This proposal aims to identify a novel neural stem cell population in the adult mammalian hypothalamus. We found that in the adult mouse hypothalamus there is a small population of cells, which expresses the nuclear receptor protein Tlx and can give rise to new neurons when exposed to growth factors in vivo. This strongly suggests that the Tlx expressing cells are the origin of new neurons in the adult hypothalamus. We will first analyze the microenvironment of these Tlx expressing cells and their potential to generate different neuronal subtypes will be investigated using the established animal models. As a NSCs determinant in the adult mouse brain, the role of Tlx will be further analyzed using gain or loss-off function. Changes and contribution of the hypothalamic NSCs during aging and brain injury will be investigated. The results and genetic tools obtained from the proposed projects will settle the basis for studying the adult hypothalamic NSCs in vivo, which will greatly increase the feasibility to investigate the significance of hypothalamic adult neurogenesis. Thus provide new insights in understanding many diseases which are related to hypothalamus dysregulation, such as obesity and aggression.