title: Wnt/β-catenin signaling regulates sequential fate decisions of murine cortical precursor cells.
abstract: 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.
authors.affiliation: Cell and Developmental Biology Division, Institute of Anatomy.
authors.forename: Kalina
authors.initials: K
authors.lastname: Draganova
authors.forename: Martina
authors.initials: M
authors.lastname: Zemke
authors.forename: Luis
authors.initials: L
authors.lastname: Zurkirchen
authors.forename: Tomas
authors.initials: T
authors.lastname: Valenta
authors.forename: Claudio
authors.initials: C
authors.lastname: Cantù
authors.forename: Michal
authors.initials: M
authors.lastname: Okoniewski
authors.forename: Marie-Theres
authors.initials: MT
authors.lastname: Schmid
authors.forename: Raymond
authors.initials: R
authors.lastname: Hoffmans
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
authors.forename: Konrad
authors.initials: K
authors.lastname: Basler
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D051176:beta Catenin
keywords: Cellular proliferation; Neural differentiation; Neural stem cell; Signal transduction