Hypothalamic radial glia function as self-renewing neural progenitors in the absence of Wnt/β-catenin signaling

Abstract

The vertebrate hypothalamus contains persistent radial glia that have been proposed to function as neural progenitors. In zebrafish, a high level of postembryonic hypothalamic neurogenesis has been observed, but the role of radial glia in generating these new neurons is unclear. We have used inducible Cre-mediated lineage labeling to show that a population of hypothalamic radial glia undergoes selfrenewal and generates multiple neuronal subtypes at larval stages. Whereas Wnt/β-catenin signaling has been demonstrated to promote the expansion of other stemand progenitorcell populations,we find that Wnt/β-catenin pathway activity inhibits this process in hypothalamic radial glia and is not required for their self-renewal. By contrast, Wnt/β- catenin signaling is required for the differentiation of a specific subset of radial glial neuronal progeny residing along the ventricular surface.We also showthat partial genetic ablationof hypothalamic radial glia or their progeny causes a net increase in their proliferation, which is also independent ofWnt/β-catenin signaling. Hypothalamic radial glia in the zebrafish larva thus exhibit several key characteristics of a neural stem cell population, and our data support the ideathatWnt pathway function may not be homogeneous in all stem or progenitor cells.