Wnt/β‐Catenin Signaling Regulates Sequential Fate Decisions of Murine Cortical Precursor CellsShow others and affiliations
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
2018-08-082018-08-082021-06-10Bibliographically approved