title: Phosphorylated β-catenin localizes to centrosomes of neuronal progenitors and is required for cell polarity and neurogenesis in developing midbrain.
abstract: β-catenin has well-established functions in cell growth and differentiation as part of the Wnt signaling pathway and in regulation of cellular adhesion with E-cadherin. Here we studied its significance in midbrain development by temporally controlled deletion of β-catenin allowing simultaneous analysis of complete (β-cat-null) and partial (β-cat-low) loss-of-function phenotypes in progenitor cells. β-cat-null cells did not contain centrosomes or a microtubule network and were unpolarized forming delaminated bulges. β-cat-low cells displayed defects in the orientation of the mitotic spindle, increased asymmetric cell divisions and premature differentiation in absence of alterations in polarity or adhesion. The spindle defect was associated with decreased centrosomal S33/S34/T41 phosphorylated β-catenin (p-β-cat) and centrosomal and microtubule defects. Interestingly, neural progenitor cells in mice expressing only unphosphorylatable β-catenin share several phenotypes with β-catenin loss-of-function mice with defects in microtubules and polarity. The results demonstrate a novel function for p-β-cat in maintaining neuroepithelial integrity and suggest that centrosomal p-ß-cat is required to maintain symmetric cleavages and polarity in neural progenitors.
authors: Institute of Biotechnology, University of Helsinki, Finland. Dmitri.chilov@helsinki.fi
authors: Dmitri
authors: D
authors: Chilov
authors: Natalia
authors: N
authors: Sinjushina
authors: Hannu
authors: H
authors: Rita
authors: Makoto M
authors: MM
authors: Taketo
authors: Tomi P
authors: TP
authors: Mäkelä
authors: Juha
authors: J
authors: Partanen
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D018385:Centrosome / Q000378:metabolism*; D004285:Dogs; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D008636:Mesencephalon / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051176:beta Catenin / Q000032:analysis / Q000378:metabolism*
chemical_list: D051176:beta Catenin