Control of tissue morphology by Fasciclin III-mediated intercellular adhesion

Morphogenesis is dependent on the orchestration of multiple developmental processes to generate mature functional organs. However, the signalling pathways that coordinate morphogenesis and the mechanisms that translate these signals into tissue shape changes are not well understood. Here, we demonstrate that changes in intercellular adhesion mediated by the transmembrane protein Fasciclin III (FasIII) represent a key mediator of morphogenesis. Using the embryonic Drosophila hindgut as an in vivo model for organogenesis, we show that the tightening of hindgut curvature that normally occurs between embryonic stage 12 and 15 to generate the characteristic shepherd’s crook shape is dependent on localised JAK/STAT pathway activation. This localised pathway activity drives the expression of FasIII leading to its subcellular lateralisation at a stage before formation of septate junctions. Additionally, we show that JAK/STAT- and FasIII-dependent morphogenesis also regulates folds within the third instar wing imaginal disc. We show that FasIII forms homophilic intercellular interactions that promote intercellular adhesion in vivo and in cultured cells. To explore these findings, we have developed a mathematical model of the developing hindgut, based on the differential interfacial tension hypothesis (DITH) linking intercellular adhesion and localised surface tension. Our model suggests that increased intercellular adhesion provided by FasIII can be sufficient to drive the tightening of tube curvature observed. Taken together, these results identify a conserved molecular mechanism that directly links JAK/STAT pathway signalling to intercellular adhesion and that sculpts both tubular and planar epithelial shape.

[1]  V. Riechmann,et al.  Tao controls epithelial morphogenesis by promoting Fasciclin 2 endocytosis , 2012, The Journal of cell biology.

[2]  Françoise Brochard-Wyart,et al.  Soft Matter Models of Developing Tissues and Tumors , 2012, Science.

[3]  Satoru Kobayashi,et al.  Glypicans regulate JAK/STAT signaling and distribution of the Unpaired morphogen , 2012, Development.

[4]  R. Fehon,et al.  Analysis of protein dynamics within the septate junction reveals a highly stable core protein complex that does not include the basolateral polarity protein Discs large , 2011, Journal of Cell Science.

[5]  T. Ando,et al.  Chirality in Planar Cell Shape Contributes to Left-Right Asymmetric Epithelial Morphogenesis , 2011, Science.

[6]  E. Smythe,et al.  Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. , 2011, Cellular signalling.

[7]  W. Stec,et al.  Negative regulation of Drosophila JAK–STAT signalling by endocytic trafficking , 2010, Journal of Cell Science.

[8]  B. Honig,et al.  Coaction of intercellular adhesion and cortical tension specifies tissue surface tension , 2010, Proceedings of the National Academy of Sciences.

[9]  Pierre-François Lenne,et al.  Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis , 2008, Nature Cell Biology.

[10]  J. Jacobs,et al.  Bmc Developmental Biology Varicose: a Maguk Required for the Maturation and Function of Drosophila Septate Junctions , 2022 .

[11]  R. Krams,et al.  Increased Endothelial Mitogen-Activated Protein Kinase Phosphatase-1 Expression Suppresses Proinflammatory Activation at Sites That Are Resistant to Atherosclerosis , 2008, Circulation research.

[12]  M. Zeidler,et al.  Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat transcription factor preferences , 2008, EMBO reports.

[13]  S. Hilgenfeldt,et al.  Physical modeling of cell geometric order in an epithelial tissue , 2008, Proceedings of the National Academy of Sciences.

[14]  Frank Jülicher,et al.  The Influence of Cell Mechanics, Cell-Cell Interactions, and Proliferation on Epithelial Packing , 2007, Current Biology.

[15]  T. Lecuit,et al.  Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis , 2007, Nature Reviews Molecular Cell Biology.

[16]  B. Dickson,et al.  A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila , 2007, Nature.

[17]  N. Perrimon,et al.  GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. , 2007, Gene expression patterns : GEP.

[18]  M. Zeidler,et al.  JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions , 2006, Development.

[19]  Stephen Brown,et al.  Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand. , 2005, Developmental biology.

[20]  R. Carthew,et al.  Adhesion proteins and the control of cell shape. , 2005, Current opinion in genetics & development.

[21]  Luis M. Escudero,et al.  Echinoid is a component of adherens junctions that cooperates with DE-Cadherin to mediate cell adhesion. , 2005, Developmental cell.

[22]  R. B. Green,et al.  The Drm–Bowl–Lin relief-of-repression hierarchy controls fore- and hindgut patterning and morphogenesis , 2003, Mechanisms of Development.

[23]  J. Lengyel,et al.  Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium , 2003, Development.

[24]  M. Zeidler,et al.  Cloning and expression of Drosophila SOCS36E and its potential regulation by the JAK/STAT pathway , 2002, Mechanisms of Development.

[25]  Piero Carninci,et al.  The Drosophila gene collection: identification of putative full-length cDNAs for 70% of D. melanogaster genes. , 2002, Genome research.

[26]  G Wayne Brodland,et al.  The Differential Interfacial Tension Hypothesis (DITH): a comprehensive theory for the self-rearrangement of embryonic cells and tissues. , 2002, Journal of biomechanical engineering.

[27]  J. Lengyel,et al.  It takes guts: the Drosophila hindgut as a model system for organogenesis. , 2002, Developmental biology.

[28]  J. Singer,et al.  drumstick, bowl, and lines are required for patterning and cell rearrangement in the Drosophila embryonic hindgut. , 2001, Developmental biology.

[29]  Stephen Brown,et al.  Identification of the first invertebrate interleukin JAK/STAT receptor, the Drosophila gene domeless , 2001, Current Biology.

[30]  M. Cybulsky,et al.  The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[31]  N. Perrimon,et al.  Polarity determination in the Drosophila eye: a novel role for unpaired and JAK/STAT signaling. , 1999, Genes & development.

[32]  C. L. Adams,et al.  Cytomechanics of cadherin-mediated cell-cell adhesion. , 1998, Current opinion in cell biology.

[33]  Prof. Dr. José A. Campos-Ortega,et al.  The Embryonic Development of Drosophila melanogaster , 1997, Springer Berlin Heidelberg.

[34]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[35]  N. Perrimon,et al.  Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. , 1995, The EMBO journal.

[36]  H. Luo,et al.  An amino acid substitution in the Drosophila hopTum‐l Jak kinase causes leukemia‐like hematopoietic defects. , 1995, The EMBO journal.

[37]  P. Bates,et al.  PECAM-1: its expression and function as a cell adhesion molecule on hemopoietic and endothelial cells. , 1995, Leukemia & lymphoma.

[38]  P J Bryant,et al.  The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. , 1995, Genes & development.

[39]  I. Guerrero,et al.  Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. , 1994, The EMBO journal.

[40]  V. Hartenstein,et al.  The development of cellular junctions in the Drosophila embryo. , 1994, Developmental biology.

[41]  Yasuji Sawada,et al.  Can Surface Adhesion Drive Cell Rearrangement? Part II: A Geometrical Model , 1993 .

[42]  François Graner,et al.  Can Surface Adhesion Drive Cell-rearrangement? Part I: Biological Cell-sorting , 1993 .

[43]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[44]  Glazier,et al.  Simulation of biological cell sorting using a two-dimensional extended Potts model. , 1992, Physical review letters.

[45]  D. Lindsley,et al.  The Genome of Drosophila Melanogaster , 1992 .

[46]  C. Goodman,et al.  Fasciclin III: A novel homophilic adhesion molecule in Drosophila , 1989, Cell.

[47]  I. Schneider,et al.  Cell lines derived from late embryonic stages of Drosophila melanogaster. , 1972, Journal of embryology and experimental morphology.

[48]  G. Rubin,et al.  The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes , 2004 .

[49]  R. Lehmann,et al.  In situ hybridization to RNA. , 1994, Methods in cell biology.

[50]  V. Hartenstein.  Atlas of Drosophila development , 1993 .

[51]  Kenneth A. Brakke,et al.  The Surface Evolver , 1992, Exp. Math..