Hedgehog signaling regulates neurogenesis in the larval and adult zebrafish hypothalamus

Abstract

While neurogenesis in the adult hypothalamus is now known to be essential for proper function, the cell-cell signaling events that regulate neurogenesis in this evolutionarily conserved brain region remain poorly understood. Here we show that Hedgehog (Hh)/Gli signaling positively regulates hypothalamic neurogenesis in both larval and adult zebrafish and is necessary and sufficient for normal hypothalamic proliferation rates. Hedgehog-responsive cells are relatively rapidly proliferating pluripotent neural precursors that give rise to dopaminergic, serotonergic, and GABAergic neurons. in situ and transgenic reporter analyses revealed substantial heterogeneity in cell-cell signaling within the hypothalamic niche, with slow cycling Nestin-expressing cells residing among distinct and overlapping populations of Sonic Hh (Shh)-expressing, Hh-responsive, Notch-responsive, and Wnt-responsive radial glia. This work shows for the first time that Hh/Gli-signaling is a key component of the complex cell-cell signaling environment that regulates hypothalamic neurogenesis throughout life.