First Author | Draganova K | Year | 2015 |
Journal | Stem Cells | Volume | 33 |
Issue | 1 | Pages | 170-82 |
PubMed ID | 25182747 | Mgi Jnum | J:274335 |
Mgi Id | MGI:6287730 | Doi | 10.1002/stem.1820 |
Citation | Draganova K, et al. (2015) Wnt/beta-catenin signaling regulates sequential fate decisions of murine cortical precursor cells. Stem Cells 33(1):170-82 |
abstractText | 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. beta-Catenin transduces extracellular Wnt signals, but also maintains adherens junctions integrity. Here, we identify for the first time the contribution of beta-catenin transcriptional activity as opposed to its adhesion role in the development of the cerebral cortex by combining a novel beta-catenin mutant allele with conditional inactivation approaches. Wnt/beta-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/beta-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/beta-catenin signaling-ablated cortex. Thus, beta-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. |