Polychaetoid controls patterning by modulating adhesion in the Drosophila pupal retina.

Correct cellular patterning is central to tissue morphogenesis, but the role of epithelial junctions in this process is not well-understood. The Drosophila pupal eye provides a sensitive and accessible model for testing the role of junction-associated proteins in cells that undergo dynamic and coordinated movements during development. Mutations in polychaetoid (pyd), the Drosophila homologue of Zonula Occludens-1, are characterized by two phenotypes visible in the adult fly: increased sensory bristle number and the formation of a rough eye produced by poorly arranged ommatidia. We found that Pyd was localized to the adherens junction in cells of the developing pupal retina. Reducing Pyd function in the pupal eye resulted in mis-patterning of the interommatidial cells and a failure to consistently switch cone cell contacts from an anterior-posterior to an equatorial-polar orientation. Levels of Roughest, DE-Cadherin and several other adherens junction-associated proteins were increased at the membrane when Pyd protein was reduced. Further, both over-expression and mutations in several junction-associated proteins greatly enhanced the patterning defects caused by reduction of Pyd. Our results suggest that Pyd modulates adherens junction strength and Roughest-mediated preferential cell adhesion.

[1]  S. Gorski,et al.  A screen for dominant modifiers of the irreC-rst cell death phenotype in the developing Drosophila retina. , 2000, Genetics.

[2]  K. Tryggvason,et al.  The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. , 2001, Human molecular genetics.

[3]  R. Cagan,et al.  Fast cloning inverted repeats for RNA interference. , 2006, RNA.

[4]  Zhiping Nie,et al.  Restricted expression of the irreC-rst protein is required for normal axonal projections of columnar visual neurons , 1995, Neuron.

[5]  K. Fischbach,et al.  Reorganization of membrane contacts prior to apoptosis in the Drosophila retina: the role of the IrreC-rst protein. , 1996, Development.

[6]  U. Tepass,et al.  Adherens junctions in Drosophila retinal morphogenesis. , 2007, Trends in cell biology.

[7]  R. Murphey,et al.  Isolation of mutations affecting neural circuitry required for grooming behavior in Drosophila melanogaster. , 1993, Genetics.

[8]  R. Ueda,et al.  The Drosophila tamou gene, a component of the activating pathway of extramacrochaetae expression, encodes a protein homologous to mammalian cell-cell junction-associated protein ZO-1. , 1996, Genes & development.

[9]  D. Kerjaschki.  Caught flat-footed: podocyte damage and the molecular bases of focal glomerulosclerosis. , 2001, The Journal of clinical investigation.

[10]  T Wolff,et al.  Cell death in normal and rough eye mutants of Drosophila. , 1991, Development.

[11]  J. Knoblich,et al.  DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila , 2000, Nature Cell Biology.

[12]  M. Itoh,et al.  Involvement of ZO-1 in Cadherin-based Cell Adhesion through Its Direct Binding to α Catenin and Actin Filaments , 1997, The Journal of cell biology.

[13]  C. Doe,et al.  Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia , 2003, The Journal of cell biology.

[14]  T. Uemura,et al.  A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. , 1994, Developmental biology.

[15]  D. Bredt,et al.  Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. , 2005, Annual review of biochemistry.

[16]  Y. Jan,et al.  The regulation and function of the helix-loop-helix gene, asense, in Drosophila neural precursors. , 1993, Development.

[17]  I. Macara,et al.  Depletion of E-cadherin disrupts establishment but not maintenance of cell junctions in Madin-Darby canine kidney epithelial cells. , 2006, Molecular biology of the cell.

[18]  C. Brachmann,et al.  Identification of the death zone: a spatially restricted region for programmed cell death that sculpts the fly eye , 2007, Cell Death and Differentiation.

[19]  Richard W. Carthew,et al.  Surface mechanics mediate pattern formation in the developing retina , 2004, Nature.

[20]  T. Uemura,et al.  Axon Patterning Requires D N-cadherin, a Novel Neuronal Adhesion Receptor, in the Drosophila Embryonic CNS , 1997, Neuron.

[21]  M. Itoh,et al.  Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion. , 1999 .

[22]  R. Fehon,et al.  Epithelial cell polarity and cell junctions in Drosophila. , 2001, Annual review of genetics.

[23]  S. Benzer,et al.  Development of the Drosophila retina, a neurocrystalline lattice. , 1976, Developmental biology.

[24]  A. Forge,et al.  Tricellulin is a tight-junction protein necessary for hearing. , 2006, American journal of human genetics.

[25]  Stuart K. Kim,et al.  The LIN-2/LIN-7/LIN-10 Complex Mediates Basolateral Membrane Localization of the C. elegans EGF Receptor LET-23 in Vulval Epithelial Cells , 1998, Cell.

[26]  V. Hartenstein,et al.  shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia. , 1996, Genes & development.

[27]  H. Ward,et al.  Tight junction biology and kidney dysfunction. , 2006, American journal of physiology. Renal physiology.

[28]  D. Larson,et al.  Csk-deficient boundary cells are eliminated from normal Drosophila epithelia by exclusion, migration, and apoptosis. , 2006, Developmental cell.

[29]  P. S. St. John,et al.  Nephrin localizes to the slit pore of the glomerular epithelial cell. , 1999, Kidney international.

[30]  T. Uemura,et al.  Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein , 1993, The Journal of cell biology.

[31]  R. Cagan.  The signals that drive kidney development: a view from the fly eye , 2003, Current opinion in nephrology and hypertension.

[32]  D L Rimm,et al.  Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[33]  A. Ávila-Flores,et al.  MAGUK proteins: structure and role in the tight junction. , 2000, Seminars in cell & developmental biology.

[34]  M. Itoh,et al.  The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy , 1993, The Journal of cell biology.

[35]  M. Farquhar,et al.  Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin. , 2004, The American journal of pathology.

[36]  B. Schermer,et al.  The Carboxyl Terminus of Neph Family Members Binds to the PDZ Domain Protein Zonula Occludens-1* , 2003, The Journal of Biological Chemistry.

[37]  Ross L Cagan,et al.  Patterning the fly eye: the role of apoptosis. , 2003, Trends in genetics : TIG.

[38]  M. Itoh,et al.  Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins , 1999, The Journal of cell biology.

[39]  M. Itoh,et al.  Characterization of ZO-2 as a MAGUK Family Member Associated with Tight as well as Adherens Junctions with a Binding Affinity to Occludin and α Catenin* , 1999, The Journal of Biological Chemistry.

[40]  T. Matsui,et al.  Establishment and Characterization of Cultured Epithelial Cells Lacking Expression of ZO-1* , 2004, Journal of Biological Chemistry.

[41]  Ross Cagan,et al.  Preferential adhesion mediated by Hibris and Roughest regulates morphogenesis and patterning in the Drosophila eye. , 2005, Developmental cell.

[42]  A. Rajasekaran,et al.  Catenins and zonula occludens-1 form a complex during early stages in the assembly of tight junctions , 1996, The Journal of cell biology.

[43]  E. Wieschaus,et al.  Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless , 1990, Cell.

[44]  M. Sheng,et al.  Essential Role for dlg in Synaptic Clustering of Shaker K+ Channels In Vivo , 1997, The Journal of Neuroscience.

[45]  E. Wieschaus,et al.  Junctions as Organizing Centers in Epithelial Cells? A Fly Perspective , 2002, Traffic.

[46]  S. Tsukita,et al.  Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells , 2005, The Journal of cell biology.

[47]  M. Balda,et al.  Tight junctions: molecular architecture and function. , 2006, International Review of Cytology.

[48]  H. Ellis,et al.  Localization of the Drosophila MAGUK protein Polychaetoid is controlled by alternative splicing , 2001, Mechanisms of Development.

[49]  B. Gumbiner,et al.  Regulation of cadherin-mediated adhesion in morphogenesis , 2005, Nature Reviews Molecular Cell Biology.

[50]  James M. Anderson,et al.  The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium , 1990, The Journal of cell biology.

[51]  Richard D Fetter,et al.  Regulation of Postsynaptic Structure and Protein Localization by the Rho-Type Guanine Nucleotide Exchange Factor dPix , 2001, Neuron.

[52]  R. Ramirez-Solis,et al.  Proteinuria and Perinatal Lethality in Mice Lacking NEPH1, a Novel Protein with Homology to NEPHRIN , 2001, Molecular and Cellular Biology.

[53]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[54]  Norbert Perrimon,et al.  Molecular mechanisms of epithelial morphogenesis. , 2002, Annual review of cell and developmental biology.

[55]  D. Kerjaschki,et al.  Nephrin and Neph1 Co-localize at the Podocyte Foot Process Intercellular Junction and Form cis Hetero-oligomers* , 2003, Journal of Biological Chemistry.

[56]  M. Kretzler,et al.  The glomerular slit diaphragm is a modified adherens junction. , 2000, Journal of the American Society of Nephrology : JASN.

[57]  W. Weis,et al.  Re-solving the Cadherin-Catenin-Actin Conundrum* , 2006, Journal of Biological Chemistry.

[58]  P. Bryant,et al.  Localization of proteins to the apico-lateral junctions of Drosophila epithelia. , 1997, Developmental genetics.

[59]  R. Cagan,et al.  The emergence of order in the Drosophila pupal retina. , 1989, Developmental biology.

[60]  S. Tsukita,et al.  Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization , 2007, The Journal of cell biology.

[61]  S. Tsukita,et al.  Dynamic features of adherens junctions during Drosophila embryonic epithelial morphogenesis revealed by a Dα-catenin-GFP fusion protein , 1999, Development Genes and Evolution.

[62]  David E Larson,et al.  Dynamic Decapentaplegic signaling regulates patterning and adhesion in the Drosophila pupal retina , 2007, Development.

[63]  D. Yamamoto,et al.  The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. , 1997, Development.

[64]  L Peltonen,et al.  Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. , 1998, Molecular cell.

[65]  Hj. Müller.  Genetic control of epithelial cell polarity: Lessons from Drosophila , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[66]  L. Gu,et al.  ZO-3, a Novel Member of the MAGUK Protein Family Found at the Tight Junction, Interacts with ZO-1 and Occludin , 1998, The Journal of cell biology.

[67]  R. Ueda,et al.  Direct binding between two PDZ domain proteins Canoe and ZO-1 and their roles in regulation of the Jun N-terminal kinase pathway in Drosophila morphogenesis , 1998, Mechanisms of Development.

[68]  Evelyn Mack Truitt.  On Screen , 1974 .

[69]  S. Lindquist,et al.  The FLP recombinase of yeast catalyzes site-specific recombination in the drosophila genome , 1989, Cell.

[70]  U. Certa,et al.  Polychaetoid/ZO-1 Is Required for Cell Specification and Rearrangement during Drosophila Tracheal Morphogenesis , 2006, Current Biology.

[71]  J. Freedman,et al.  polychaetoid is required to restrict segregation of sensory organ precursors from proneural clusters in Drosophila , 1996, Mechanisms of Development.

[72]  E. Knust,et al.  IrreC/rst-mediated cell sorting during Drosophila pupal eye development depends on proper localisation of DE-cadherin , 2005, Development.

[73]  Ulrich Tepass,et al.  Drosophila oocyte localization is mediated by differential cadherin-based adhesion , 1998, Nature.

[74]  R. Cagan,et al.  Cell fate specification in the developing Drosophila retina. , 1993, Development (Cambridge, England). Supplement.

[75]  T. Matsui,et al.  ZO-1 and ZO-2 Independently Determine Where Claudins Are Polymerized in Tight-Junction Strand Formation , 2006, Cell.

[76]  A. Jarman,et al.  Echinoid facilitates Notch pathway signalling during Drosophila neurogenesis through functional interaction with Delta , 2003, Development.

[77]  P. Bryant,et al.  Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia , 1996, The Journal of cell biology.

[78]  R. Malinow,et al.  PSD-95 is required for activity-driven synapse stabilization , 2007, Proceedings of the National Academy of Sciences.

[79]  R. Cagan,et al.  Programmed cell death and patterning in Drosophila , 2000, Cell Death and Differentiation.