Cell interactions and planar polarity in the abdominal epidermis of Drosophila

The integument of the Drosophila adult abdomen bears oriented hairs and bristles that indicate the planar polarity of the epidermal cells. We study four polarity genes, frizzled (fz), prickle (pk), Van gogh/strabismus (Vang/stbm) and starry night/flamingo (stan/fmi), and note what happens when these genes are either removed or overexpressed in clones of cells. The edges of the clones are interfaces between cells that carry different amounts of gene products, interfaces that can cause reversals of planar polarity in the clone and wild-type cells outside them. To explain, we present a model that builds on our earlier picture of a gradient of X, the vector of which specifies planar polarity and depends on two cadherin proteins, Dachsous and Fat. We conjecture that the X gradient is read out, cell by cell, as a scalar value of Fz activity, and that Pk acts in this process, possibly to determine the sign of the Fz activity gradient. We discuss evidence that cells can compare their scalar readout of the level of X with that of their neighbours and can set their own readout towards an average of those. This averaging, when it occurs near the edges of clones, changes the scalar response of cells inside and outside the clones, leading to new vectors that change polarity. The results argue that Stan must be present in both cells being compared and acts as a conduit between them for the transfer of information. And also that Vang assists in the receipt of this information. The comparison between neighbours is crucial, because it gives the vector that orients hairs – these point towards the neighbour cell that has the lowest level of Fz activity. Recently, it has been shown that, for a limited period shortly before hair outgrowth in the wing, the four proteins we study, as well as others, become asymmetrically localised in the cell membrane, and this process is thought to be instrumental in the acquisition of cell polarity. However, some results do not fit with this view – we suggest that these localisations may be more a consequence than a cause of planar polarity.

[1]  D. Strutt.  Asymmetric localization of frizzled and the establishment of cell polarity in the Drosophila wing. , 2001, Molecular cell.

[2]  D. Tree,et al.  The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs. , 1999, Genes & development.

[3]  Jeremy Nathans,et al.  A new member of the frizzled family from Drosophila functions as a Wingless receptor , 1996, Nature.

[4]  J. Taylor,et al.  Van Gogh: a new Drosophila tissue polarity gene. , 1998, Genetics.

[5]  P. Adler,et al.  The frizzled gene of Drosophila encodes a membrane protein with an odd number of transmembrane domains , 1994, Mechanisms of Development.

[6]  J. Axelrod,et al.  Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. , 2001, Genes & development.

[7]  S. Eaton,et al.  The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. , 2001, Developmental cell.

[8]  M. Wehrli,et al.  Independent regulation of anterior/posterior and equatorial/polar polarity in the Drosophila eye; evidence for the involvement of Wnt signaling in the equatorial/polar axis. , 1998, Development.

[9]  N. Perrimon,et al.  The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. , 1994, Genes & development.

[10]  David Strutt,et al.  Cleavage and secretion is not required for Four-jointed function in Drosophila patterning , 2004, Development.

[11]  R. Arkowitz,et al.  Responding to attraction: chemotaxis and chemotropism in Dictyostelium and yeast. , 1999, Trends in cell biology.

[12]  P. Adler,et al.  Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila , 1987, Nature.

[13]  Marek Mlodzik,et al.  Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? , 2002, Trends in genetics : TIG.

[14]  P. Laurent-Puig.  [Cell polarity]. , 1990, Gastroenterologie clinique et biologique.

[15]  The FlyBase database of the Drosophila genome projects and community literature. , 2003, Nucleic acids research.

[16]  W. Strapps,et al.  Linking Frizzled and Wnt signaling in Drosophila development. , 1997, Development.

[17]  Howard C. Berg,et al.  Genetic analysis , 1957, Nature Biotechnology.

[18]  David Strutt,et al.  Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled. , 2002, Developmental cell.

[19]  S. Zigmond,et al.  Mechanisms of sensing chemical gradients by polymorphonuclear leukocytes , 1974, Nature.

[20]  R. Nusse,et al.  Mechanisms of Wnt signaling in development. , 1998, Annual review of cell and developmental biology.

[21]  H. Theisen,et al.  dishevelled is required during wingless signaling to establish both cell polarity and cell identity. , 1994, Development.

[22]  J. Charlton,et al.  The domineering non-autonomy of frizzled and Van Gogh clones in the Drosophila wing is a consequence of a disruption in local signaling , 2000, Mechanisms of Development.

[23]  Jeffrey D. Axelrod,et al.  Regulation of Frizzled by Fat-like Cadherins during Planar Polarity Signaling in the Drosophila Compound Eye , 2002, Cell.

[24]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

[25]  J. Charlton,et al.  The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. , 1999, Development.

[26]  P. Adler,et al.  Tissue polarity points from cells that have higher Frizzled levels towards cells that have lower Frizzled levels , 1997, Current Biology.

[27]  P. Lawrence,et al.  hedgehog and engrailed: pattern formation and polarity in the Drosophila abdomen. , 1999, Development.

[28]  Jeffrey D. Axelrod,et al.  Fidelity in planar cell polarity signalling , 2003, Nature.

[29]  Yasuyuki Shima,et al.  Flamingo, a Seven-Pass Transmembrane Cadherin, Regulates Planar Cell Polarity under the Control of Frizzled , 1999, Cell.

[30]  C. M. Chen,et al.  Wingless transduction by the Frizzled and Frizzled2 proteins of Drosophila. , 1999, Development.

[31]  G. Golderer,et al.  Nitric oxide synthase is induced in sporulation of Physarum polycephalum. , 2001, Genes & development.

[32]  P. Adler,et al.  Molecular structure of frizzled, a Drosophila tissue polarity gene. , 1990, Genetics.

[33]  P. Lawrence.  Gradients in the Insect Segment: The Orientation of Hairs in the Milkweed Bug Oncopeltus Fasciatus , 1966 .

[34]  Thomas Lecuit,et al.  slam encodes a developmental regulator of polarized membrane growth during cleavage of the Drosophila embryo. , 2002, Developmental cell.

[35]  T. Uemura,et al.  Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization , 2001, Current Biology.

[36]  P. Lawrence,et al.  Towards a model of the organisation of planar polarity and pattern in the Drosophila abdomen. , 2002, Development.

[37]  J. Zhang,et al.  frizzled regulates mirror-symmetric pattern formation in the Drosophila eye. , 1995, Development.

[38]  J. Charlton,et al.  Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling. , 1998, Development.

[39]  K. Nübler-Jung,et al.  Cell polarity during wound healing in an insect epidermis. , 1987, Development.

[40]  H. Pelham,et al.  Slow Diffusion of Proteins in the Yeast Plasma Membrane Allows Polarity to Be Maintained by Endocytic Cycling , 2003, Current Biology.

[41]  R. Bastock,et al.  Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning , 2003, Development.

[42]  P. Lawrence,et al.  Hedgehog organises the pattern and polarity of epidermal cells in the Drosophila abdomen. , 1997, Development.

[43]  D. Strutt,et al.  The asymmetric subcellular localisation of components of the planar polarity pathway. , 2002, Seminars in cell & developmental biology.

[44]  Y. Jan,et al.  Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila , 1999, Current Biology.

[45]  P. Lawrence,et al.  The hedgehog morphogen and gradients of cell affinity in the abdomen of Drosophila. , 1999, Development.

[46]  P. Adler,et al.  Planar signaling and morphogenesis in Drosophila. , 2002, Developmental cell.

[47]  M. Scott,et al.  Prickle Mediates Feedback Amplification to Generate Asymmetric Planar Cell Polarity Signaling , 2002, Cell.

[48]  C. Parent,et al.  A cell's sense of direction. , 1999, Science.

[49]  M. Bretscher.  Endocytosis: relation to capping and cell locomotion. , 1984, Science.

[50]  J. Nathans,et al.  Frizzled and Dfrizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development. , 1999, Development.

[51]  G. Rubin,et al.  Strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila. , 1998, Development.

[52]  Scott E Fraser,et al.  Convergent extension: the molecular control of polarized cell movement during embryonic development. , 2002, Developmental cell.

[53]  H. F. STUMPF,et al.  Mechanism by which Cells estimate their Location within the Body , 1966, Nature.

[54]  P. Lawrence,et al.  Developmental Compartments and Planar Polarity in Drosophila , 2002, Current Biology.

[55]  D. Gubb,et al.  A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. , 1982, Journal of embryology and experimental morphology.

[56]  P. Lawrence,et al.  Hedgehog acts by distinct gradient and signal relay mechanisms to organise cell type and cell polarity in the Drosophila abdomen. , 1997, Development.

[57]  Julian Lewis,et al.  Planar cell polarity in the inner ear: how do hair cells acquire their oriented structure? , 2002, Journal of neurobiology.