Multicellular rosette formation links planar cell polarity to tissue morphogenesis.

Developmental Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA.
Developmental Cell (Impact Factor: 10.37). 11/2006; 11(4):459-70. DOI: 10.1016/j.devcel.2006.09.007
Source: PubMed

ABSTRACT Elongation of the body axis is accompanied by the assembly of a polarized cytoarchitecture that provides the basis for directional cell behavior. We find that planar polarity in the Drosophila embryo is established through a sequential enrichment of actin-myosin cables and adherens junction proteins in complementary surface domains. F-actin accumulation at AP interfaces represents the first break in planar symmetry and occurs independently of proper junctional protein distribution at DV interfaces. Polarized cells engage in a novel program of locally coordinated behavior to generate multicellular rosette structures that form and resolve in a directional fashion. Actin-myosin structures align across multiple cells during rosette formation, and adherens junction proteins assemble in a stepwise fashion during rosette resolution. Patterning genes essential for axis elongation selectively affect the frequency and directionality of rosette formation. We propose that the generation of higher-order rosette structures links local cell interactions to global tissue reorganization during morphogenesis.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Force-producing convergence (narrowing) and extension (lengthening) of tissues by active intercalation of cells along the axis of convergence play a major role in axial morphogenesis during embryo development in both vertebrates and invertebrates, and failure of these processes in human embryos leads to defects including spina bifida and anencephaly. Here we use Xenopus laevis, a system in which the polarized cell motility that drives this active cell intercalation has been related to the development of forces that close the blastopore and elongate the body axis, to examine the role of myosin IIB in convergence and extension. We find that myosin IIB is localized in the cortex of intercalating cells, and show by morpholino knockdown that this myosin isoform is essential for the maintenance of a stereotypical, cortical actin cytoskeleton as visualized with time-lapse fluorescent confocal microscopy. We show that this actin network consists of foci or nodes connected by cables and is polarized relative to the embryonic axis, preferentially cyclically shortening and lengthening parallel to the axis of cell polarization, elongation and intercalation, and also parallel to the axis of convergence forces during gastrulation. Depletion of MHC-B results in disruption of this polarized cytoskeleton, loss of the polarized protrusive activity characteristic of intercalating cells, eventual loss of cell-cell and cell-matrix adhesion, and dose-dependent failure of blastopore closure, arguably because of failure to develop convergence forces parallel to the myosin IIB-dependent dynamics of the actin cytoskeleton. These findings bridge the gap between a molecular-scale motor protein and tissue-scale embryonic morphogenesis.
    Development 08/2008; 135(14):2435-44. DOI:10.1242/dev.014704 · 6.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is universally accepted that genetic control over basic aspects of cell and molecular biology is the primary organizing principle in development and homeostasis of living systems. However, instances do exist where important aspects of biological order arise without explicit genetic instruction, emerging instead from simple physical principles, stochastic processes, or the complex self-organizing interaction between random and seemingly unrelated parts. Being mostly resistant to direct genetic dissection, the analysis of such emergent processes falls into a grey area between mathematics, physics and molecular cell biology and therefore remains very poorly understood. We recently proposed a mathematical model predicting the emergence of a specific non-Gaussian distribution of polygonal cell shapes from the stochastic cell division process in epithelial cell sheets; this cell shape distribution appears to be conserved across a diverse set of animals and plants.1 The use of such topological models to study the process of cellular morphogenesis has a long history, starting almost a century ago, and many insights from those original works influence current experimental studies. Here we review current and past literature on this topic while exploring some new ideas on the origins and implications of topological order in proliferating epithelia.
    BioEssays 03/2008; 30(3):260-6. DOI:10.1002/bies.20722 · 4.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Remodeling epithelia is a primary driver of morphogenesis. Here, we report a central role of myosin II in regulating several aspects of complex epithelial architecture in the Drosophila eye imaginal disc. The epithelial indentation of the morphogenetic furrow is established from a pattern of myosin II activation defined by the developmental signals Hedgehog and Decapentaplegic. More generally, patterned myosin activation can control diverse three-dimensional epithelial sculpting. We have developed a technique to image eye disc development in real time, and we show that myosin II also regulates higher-order organization of cells in the plane of the epithelium. This includes the clustering of cells into ommatidial units and their subsequent coordinated rotation. This later clustering function of myosin II depends on EGF receptor signaling. Our work implies that regulation of the actomyosin cytoskeleton can control morphogenesis by regulating both individual cell shapes and their complex two-dimensional arrangement within epithelia.
    Developmental Cell 12/2007; 13(5):717-29. DOI:10.1016/j.devcel.2007.09.002 · 10.37 Impact Factor


Available from