Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Despite our understanding of actomyosin function in individual migrating cells, we know little about the mechanisms by which actomyosin drives collective cell movement in vertebrate embryos. The collective movements of convergent extension drive both global reorganization of the early embryo and local remodeling during organogenesis. We report here that planar cell polarity (PCP) proteins control convergent extension by exploiting an evolutionarily ancient function of the septin cytoskeleton. By directing septin-mediated compartmentalization of cortical actomyosin, PCP proteins coordinate the specific shortening of mesenchymal cell-cell contacts, which in turn powers cell interdigitation. These data illuminate the interface between developmental signaling systems and the fundamental machinery of cell behavior and should provide insights into the etiology of human birth defects, such as spina bifida and congenital kidney cysts.
Fig. 1 Myosin-mediated cell cortex tension is planar polarized in Xenopus mesoderm.
(A to A″) pMyoII immunostaining of notochord in vivo (scale bar indicates 20 μm). (B) Illustration defining t- and v-type junctions and vertex angle ϕ (gray, ϕ for v-junction; red, ϕ of t-junction). A, anterior; P, posterior; M; medial; L, lateral. (C) Normalized intensity of pMyoII, defined as intensity relative to the maximum (=100%) and minimum (=0%) raw intensity for each image (n = 177 for v and 221 for t; three embryos). (D) Average vertex position change after ablation. Error bars indicate SE. (E and F) Scatter plots showing correlation between tension and edge length (E) or vertex angle (F) (n = 84 for v and 24 for t; 54 embryos).
Fig. 2 Pulsed actin assembly at v-junctions during edge shortening.
(A) Mosaic expression of two colors of the actin biosensors utrophin-FP. (A′) Time-lapse after the junction in box A′. Two populations of actin are visible: bipolar lamellipodia (green, arrowheads) and actin at the v-junction (magenta, arrows). (B) Mean intensity of utrophin (Utr, pink line) at v-junctions during edge length shortening (black line). (C) Edge length change is correlated with increase of utrophin intensity (red) but not with reduction in utrophin intensity (blue) (n = 133 cycles; six explants).
Fig. 3 Sept7 compartmentalizes cortical actin dynamics.
(A) Quantification of the lateral spread of paGFP-Utr at a cell vertex or edge (fig. S10A) (*P < 0.05, **P < 0.001, ***P < 0.0001, n = 7 to 11 explants). (B) GFP-sept7 localization in explant. (B′) GFP-sept7 colocalizes with Utr–red fluorescent protein (RFP) at vertices. (C and C′) Utr-GFP normally localizes at vertices. (D and D′) Sept7 knockdown disrupts utrophin accumulation at the vertices. (E) Quantification of (C) and (D) (see also fig. S7B). Scale bar, 20 μm; error bars, SE.
Fig. 4 Sept7 controls planar polarization of cell cortex tension.
(A to A″) pMyoII immunostaining of notochord in Sept7 knockdown embryos (compare with Fig. 1A) (scale bar, 20 μm). (B and C) The normal differences in pMyoII or vertex shift after laser ablation between v- and t-junctions are lost in Sept7 morphants (Sept7-MO). For (B), n = 74 for v and 188 for t; three embryos. For (C), n = 50 for v and 28 for t; 39 explants. (D) Average vertex shift for all junctions is not changed after Sept7 knockdown but is significantly reduced by treatment with a myosin kinase inhibitor (for control, n = 108; for sept7-MO, n = 78; for ML-7, n = 36, 111 explants). n.s., not significant; error bars, SE.
Fig. 5 PCP signaling regulates Sept7 localization.
(A and A′) GFP-Sept7 localizes at vertices in control explants. (B and B′) Dominant negative dishevelled (Xdd1) promotes ectopic GFP-Sept7 localization along edges (arrowheads). (C) Quantification of GFP-Sept7 localization (control, n = 67 and six explants; Sept7-MO, n = 50 and six explants; scale bar, 20 μm) (see also fig. S7B).
Barral,
Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast.
2000, Pubmed
Barral,
Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast.
2000,
Pubmed
Bertet,
Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation.
2004,
Pubmed
Blankenship,
Multicellular rosette formation links planar cell polarity to tissue morphogenesis.
2006,
Pubmed
Ciruna,
Planar cell polarity signalling couples cell division and morphogenesis during neurulation.
2006,
Pubmed
Cui,
Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.
2013,
Pubmed
Fernandez-Gonzalez,
Myosin II dynamics are regulated by tension in intercalating cells.
2009,
Pubmed
Fernandez-Gonzalez,
Oscillatory behaviors and hierarchical assembly of contractile structures in intercalating cells.
2011,
Pubmed
Gardel,
Mechanical integration of actin and adhesion dynamics in cell migration.
2010,
Pubmed
Jessen,
Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements.
2002,
Pubmed
Karner,
Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis.
2009,
Pubmed
,
Xenbase
Keller,
Mechanisms of convergence and extension by cell intercalation.
2000,
Pubmed
Kim,
Planar cell polarity acts through septins to control collective cell movement and ciliogenesis.
2010,
Pubmed
,
Xenbase
Kim,
Punctuated actin contractions during convergent extension and their permissive regulation by the non-canonical Wnt-signaling pathway.
2011,
Pubmed
,
Xenbase
Lienkamp,
Vertebrate kidney tubules elongate using a planar cell polarity-dependent, rosette-based mechanism of convergent extension.
2012,
Pubmed
,
Xenbase
Maddox,
Anillin and the septins promote asymmetric ingression of the cytokinetic furrow.
2007,
Pubmed
Ninomiya,
Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning.
2004,
Pubmed
,
Xenbase
Nishimura,
Planar cell polarity links axes of spatial dynamics in neural-tube closure.
2012,
Pubmed
Rauzi,
Planar polarized actomyosin contractile flows control epithelial junction remodelling.
2010,
Pubmed
Rauzi,
Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis.
2008,
Pubmed
Sawyer,
A contractile actomyosin network linked to adherens junctions by Canoe/afadin helps drive convergent extension.
2011,
Pubmed
Shih,
Cell motility driving mediolateral intercalation in explants of Xenopus laevis.
1992,
Pubmed
,
Xenbase
Skoglund,
Convergence and extension at gastrulation require a myosin IIB-dependent cortical actin network.
2008,
Pubmed
,
Xenbase
Solnica-Krezel,
Gastrulation: making and shaping germ layers.
2012,
Pubmed
Tada,
Convergent extension: using collective cell migration and cell intercalation to shape embryos.
2012,
Pubmed
,
Xenbase
Vicente-Manzanares,
Non-muscle myosin II takes centre stage in cell adhesion and migration.
2009,
Pubmed
Wallingford,
The continuing challenge of understanding, preventing, and treating neural tube defects.
2013,
Pubmed
Wallingford,
Planar cell polarity and the developmental control of cell behavior in vertebrate embryos.
2012,
Pubmed
Wallingford,
Dishevelled controls cell polarity during Xenopus gastrulation.
2000,
Pubmed
,
Xenbase
Winter,
Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton.
2001,
Pubmed
Yin,
Cooperation of polarized cell intercalations drives convergence and extension of presomitic mesoderm during zebrafish gastrulation.
2008,
Pubmed
Zallen,
Patterned gene expression directs bipolar planar polarity in Drosophila.
2004,
Pubmed
