Cofilin and Vangl2 cooperate in the initiation of planar cell polarity in the mouse embryo Journal Article

Authors: Mahaffey, J. P.; Grego Bessa, J.; Liem, K. F.; Anderson, K. V.
Article Title: Cofilin and Vangl2 cooperate in the initiation of planar cell polarity in the mouse embryo
Abstract: The planar cell polarity (PCP; non-canonical Wnt) pathway is required to orient the cells within the plane of an epithelium. Here, we show that cofilin 1 (Cfl1), an actin-severing protein, and Vangl2, a core PCP protein, cooperate to control PCP in the early mouse embryo. Two aspects of planar polarity can be analyzed quantitatively at cellular resolution in the mouse embryo: convergent extension of the axial midline; and posterior positioning of cilia on cells of the node. Analysis of the spatial distribution of brachyury+ midline cells shows that the Cfl1 mutant midline is normal, whereas Vangl2 mutants have a slightly wider midline. By contrast, midline convergent extension fails completely in Vangl2 Cfl1 double mutants. Planar polarity is required for the posterior positioning of cilia on cells in the mouse node, which is essential for the initiation of left-right asymmetry. Node cilia are correctly positioned in Cfl1 and Vangl2 single mutants, but cilia remain in the center of the cell in Vangl2 Cfl1 double mutants, leading to randomization of left-right asymmetry. In both the midline and node, the defect in planar polarity in the double mutants arises because PCP protein complexes fail to traffic to the apical cell membrane, although other aspects of apical-basal polarity are unaffected. Genetic and pharmacological experiments demonstrate that F-actin remodeling is essential for the initiation, but not maintenance, of PCP. We propose that Vangl2 and cofilin cooperate to target Rab11+ vesicles containing PCP proteins to the apical membrane during the initiation of planar cell polarity. © 2013. Published by The Company of Biologists Ltd.
Keywords: mouse; cilia; left-right patterning; planar polarity; convergent extension; axial midline; myosin light chain; rab11
Journal Title: Development
Volume: 140
Issue: 6
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2013-03-01
Start Page: 1262
End Page: 1271
Language: English
DOI: 10.1242/dev.085316
PROVIDER: scopus
PMCID: PMC3585660
PUBMED: 23406901
Notes: --- - "Export Date: 1 April 2013" - "CODEN: DEVPE" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Karel F Liem
    12 Liem
  2. Kathryn Anderson
    148 Anderson