Open AccessWnt/β‐Catenin Signaling Regulates Sequential Fate Decisions of Murine Cortical Precursor Cells
Author(s) -
Draganova Kalina,
Zemke Martina,
Zurkirchen Luis,
Valenta Tomas,
Cantù Claudio,
Okoniewski Michal,
Schmid MarieTheres,
Hoffmans Raymond,
Götz Magdalena,
Basler Konrad,
Sommer Lukas
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1820
Subject(s) - wnt signaling pathway , biology , progenitor cell , microbiology and biotechnology , corticogenesis , progenitor , neural stem cell , cell fate determination , adherens junction , catenin , beta catenin , forebrain , neurogenesis , cellular differentiation , signal transduction , stem cell , neuroscience , cadherin , genetics , cell , transcription factor , gene , central nervous system
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. S tem C ells 2015;33:170–182