Intrinsic and Extrinsic factors regulating neurogenic competence in hypothalamic tanycytes

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Hypothalamic tanycytes have limited postnatal neurogenic competence, but the extrinsic and intrinsic factors that promote this are not well understood. My predoctoral research identified a defined developmental window during which neurogenic competence is lost from hypothalamic tanycytes. I have also identified the neurogenic bHLH transcription factor Ascl1 as a candidate activator of neurogenic competence in tanycytes and identified Shh signaling as potentially promoting the survival of tanycyte-derived neurons. In the F99 phase of this award, I will investigate whether AAV-mediated overexpression of Ascl1 induces neurogenic competence and whether Shh signaling promotes the survival of tanycyte-derived neurons using cell-specific conditional genetic approaches. During the K00 phase, I will pursue postdoctoral training using zebrafish as a model to identify gene regulatory networks controlling injury-induced hypothalamic neural regeneration, identifying yet uncharacterized extrinsic and intrinsic mechanisms that regulate neurogenic competence in tanycyte-like radial glial cells. By comparing these findings to data obtained from mammalian tanycytes, I plan to identify both positive and negative regulators of neurogenic competence that could be manipulated to induce the tanycyte-derived generation of specific hypothalamic neuronal cell types for treatment of metabolic and other homeostatic disorders. These opportunities will advance my career as a neuroscientist and prepare me for a principal investigator role at an R1 institution studying tanycyte biology and hypothalamic regeneration.