title: Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis.
abstract: Neural stem cells (NSCs) generate new granule cells throughout life in the mammalian hippocampus. Canonical Wnt signaling regulates the differentiation of NSCs towards the neuronal lineage. Here we identified the prospero-related homeodomain transcription factor Prox1 as a target of β-catenin-TCF/LEF signaling in vitro and in vivo. Prox1 overexpression enhanced neuronal differentiation whereas shRNA-mediated knockdown of Prox1 impaired the generation of neurons in vitro and within the hippocampal niche. In contrast, Prox1 was not required for survival of adult-generated granule cells after they had matured, suggesting a role for Prox1 in initial granule cell differentiation but not in the maintenance of mature granule cells. The data presented here characterize a molecular pathway from Wnt signaling to a transcriptional target leading to granule cell differentiation within the adult brain and identify a stage-specific function for Prox1 in the process of adult neurogenesis.
authors: Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology Zurich, 8093 Zurich, Switzerland.
authors: Ozlem
authors: O
authors: Karalay
authors: Kathrin
authors: K
authors: Doberauer
authors: Krishna C
authors: KC
authors: Vadodaria
authors: Marlen
authors: M
authors: Knobloch
authors: Lucia
authors: L
authors: Berti
authors: Amaya
authors: A
authors: Miquelajauregui
authors: Manuela
authors: M
authors: Schwark
authors: Ravi
authors: R
authors: Jagasia
authors: Makoto M
authors: MM
authors: Taketo
authors: Victor
authors: V
authors: Tarabykin
authors: D Chichung
authors: DC
authors: Lie
authors: Sebastian
authors: S
authors: Jessberger
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008156:Luciferases; D051379:Mice; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D008156:Luciferases