Hedgehog Signaling Regulates Neurogenesis in the Larval and Adult Zebrafish Hypothalamus
Ira Male, A. Tuba Ozacar, Rita R. Fagan, Matthew D. Loring, Meng‐Chieh Shen, Veronica A. Pace, Christine Devine, Grace Lawson, Alyssa Lutservitz, Rolf O. Karlstrom
Abstract
Neurogenesis is now known to play a role in adult hypothalamic function, yet the cell-cell mechanisms regulating this neurogenesis 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. Hh-responsive radial glia represent a relatively highly proliferative precursor population that gives 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.