의생명시스템학부

Hypothalamic tanycytes, radial glial cells that exhibit many features in common with neuronal progenitors, can generate small numbers of neurons in postnatal hypothalamus, but both the identity of these neurons and the molecular mechanisms controlling tanycyte-derived neurogenesis are un-known. We report that tanycyte-specific disruption of the NFI family tran-scription factors Nfia/b/x in neonates, and to a lesser extent adults, stimu-lates proliferation and tanycyte-derived neurogenesis. Single cell RNA and ATAC-Seq analysis reveals that NFI factors repress Shh and Wnt signaling in tanycytes, and small molecule inhibitors of these pathways block prolifer-ation and tanycyte-derived neurogenesis. We show that tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes, which can mature, integrate into hypothalamic circuitry, and selectively respond to changes in internal states. These findings identify molecular mechanisms controlling tanycyte-derived neurogenesis, and identify molecular mechanisms that can be targeted to selectively remodel hypothalamic neural circuitry controlling homeostatic physiological processes and relevant to the degenerative disease.