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Wnt/β-catenin signaling regulates sequential fate decisions of murine cortical precursor cells.
Stem Cells 33, 170-182 (2015)
The fate of neural progenitor cells (NPC) 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Neural stem cell; Signal transduction; Neural differentiation; Cellular proliferation
ISSN (print) / ISBN
0737-1454
e-ISSN
1549-4918
Zeitschrift
Stem Cells
Quellenangaben
Band: 33,
Heft: 1,
Seiten: 170-182
Verlag
Wiley
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Stem Cell Research (ISF)