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Wnt/β‐Catenin Signaling Regulates Sequential Fate Decisions of Murine Cortical Precursor Cells
Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Switzerland.
Cell and Developmental Biology Division, Institute of Anatomy, Zurich, University of Zurich,Zurich, Switzerland.
Cell and Developmental Biology Division, Institute of Anatomy, Zurich, University of Zurich,Zurich, Switzerland.
Institute ofMolecular Life Sciences, Zurich, University of Zurich,Zurich, Switzerland.
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2015 (English)In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 33, no 1, p. 170-182Article in journal (Refereed) Published
Abstract [en]

The fate of neural progenitor cells (NPCs) is determined by a complex interplay of intrinsic programs and extrinsic signals, very few of which are known. β-Catenin transduces extracellular Wnt signals, but also maintains adherens junctions integrity. Here, we identify for the first time the contribution of β-catenin transcriptional activity as opposed to its adhesion role in the development of the cerebral cortex by combining a novel β-catenin mutant allele with conditional inactivation approaches. Wnt/β-catenin signaling ablation leads to premature NPC differentiation, but, in addition, to a change in progenitor cell cycle kinetics and an increase in basally dividing progenitors. Interestingly, Wnt/β-catenin signaling affects the sequential fate switch of progenitors, leading to a shortened neurogenic period with decreased number of both deep and upper-layer neurons and later, to precocious astrogenesis. Indeed, a genome-wide analysis highlighted the premature activation of a corticogenesis differentiation program in the Wnt/β-catenin signaling-ablated cortex. Thus, β-catenin signaling controls the expression of a set of genes that appear to act downstream of canonical Wnt signaling to regulate the stage-specific production of appropriate progenitor numbers, neuronal subpopulations, and astroglia in the forebrain.

Place, publisher, year, edition, pages
Durham, United States: AlphaMed Press, Inc. , 2015. Vol. 33, no 1, p. 170-182
Keywords [en]
Cellular proliferation, Neural differentiation, Neural stem cell, Signal transduction
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-150036DOI: 10.1002/stem.1820ISI: 000346494100017PubMedID: 25182747Scopus ID: 2-s2.0-84919443184OAI: oai:DiVA.org:liu-150036DiVA, id: diva2:1237288
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-08-17Bibliographically approved

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Cantù, Claudio
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