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Cited by 201Neurogenesis and neuroplasticity mechanismsWnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene Regulation

Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis

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Karalay, Özlem, Doberauer, Kathrin, Vadodaria, Krishna C., Knobloch, Marlen, Berti, Lucia, Miquelajauregui, Amaya, Schwark, Manuela, Jagasia, Ravi +4 more·2011·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1013456108PMC PMC3078392
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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.

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Cited by

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Authors
Karalay, Ö., Doberauer, K., Vadodaria, K. C., Knobloch, M., Berti, L., Miquelajauregui, A., Schwark, M., Jagasia, R., Taketo, M. M., Tarabykin, V., Lie, D. C., & Jessberger, S.
Affiliations
  • ETH Zurich (CH)
  • Helmholtz Munich (DE)
  • Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany;
  • Max Planck Institute of Experimental Medicine (DE)
  • F. Hoffmann-La Roche AG (CH)
  • Kyoto University (JP)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2011-03-21
Volume
108
Issue
14
Pages
5807-5812
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1013456108
PMC
PMC3078392
OpenAlex
W2061730618
Cited by
201
References
1
Citations by year
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FWCI
7.44
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Site cant be reached (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • National Science Foundation
  • Novartis Foundation
  • Deutsche Forschungsgemeinschaft (SFB 665)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (117744, 3100A0)
  • Eidgenössische Technische Hochschule Zürich
  • Janggen-Pöhn-Stiftung
  • Japan Society for the Promotion of Science (21229005)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Prox1, Wnt/β-catenin signaling, adult hippocampal neurogenesis, neural stem cells, granule cell differentiation, homeodomain transcription factor, neuronal differentiation, shRNA knockdown
MeSH terms
Prospero-Related Homeobox 1 Protein, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Hippocampus, Immunohistochemistry, Luciferases, Molecular Sequence Data, Blotting, Western, Signal Transduction, In Situ Hybridization, DNA Primers, Homeodomain Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Chromatin Immunoprecipitation, Wnt Proteins, Mice, Neurogenesis, Neural Stem Cells

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