title: 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 self-renewal and generates multiple neuronal subtypes at larval stages. Whereas Wnt/β-catenin signaling has been demonstrated to promote the expansion of other stem and progenitor cell 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 show that partial genetic ablation of hypothalamic radial glia or their progeny causes a net increase in their proliferation, which is also independent of Wnt/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 idea that Wnt pathway function may not be homogeneous in all stem or progenitor cells.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Duncan
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: McPherson
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Taibi
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Bonkowsky
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Douglass
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA richard.dorsky@neuro.utah.edu.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Dorsky
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D000066673:Cell Self Renewal / Q000502:physiology*; D063928:Ependymoglial Cells / Q000166:cytology*; D007031:Hypothalamus / Q000166:cytology* / Q000196:embryology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C501128:dkk1b protein, zebrafish
keywords: Hypothalamus; Neural progenitors; Radial glia; Wnt signaling; Zebrafish