The orthologous Tbx transcription factors Omb and TBX2 induce epithelial cell migration and extrusion in vivo without involvement of matrix metalloproteinases

The transcription factors TBX2 and TBX3 are overexpressed in various human cancers. Here, we investigated the effect of overexpressing the orthologous Tbx genes Drosophila optomotor-blind (omb) and human TBX2 in the epithelium of the Drosophila wing imaginal disc and observed two types of cell motility. Omb/TBX2 overexpressing cells could move within the plane of the epithelium. Invasive cells migrated long-distance as single cells retaining or regaining normal cell shape and apico-basal polarity in spite of attenuated apical DE-cadherin concentration. Inappropriate levels of DE-cadherin were sufficient to drive cell migration in the wing disc epithelium. Omb/TBX2 overexpression and reduced DE-cadherin-dependent adhesion caused the formation of actin-rich lateral cell protrusions. Omb/TBX2 overexpressing cells could also delaminate basally, penetratingthe basal lamina, however, without degradation of extracellular matrix. Expression of Timp, an inhibitor of matrix metalloproteases, blocked neither intraepithelial motility nor basal extrusion. Our results reveal an MMP-independent mechanism of cell invasion and suggest a conserved role of Tbx2-related proteins in cell invasion and metastasis-related processes.

[1]  J. Walker,et al.  Drosophila , 2020, Methods in Molecular Biology.

[2]  J. Davie,et al.  TBX2 blocks myogenesis and promotes proliferation in rhabdomyosarcoma cells , 2014, International journal of cancer.

[3]  G. Pflugfelder,et al.  Optomotor-blind in the Development of the Drosophila HS and VS Lobula Plate Tangential Cells , 2014, Journal of neurogenetics.

[4]  Keshi Chen,et al.  Tbx3 isoforms are involved in pluripotency maintaining through distinct regulation of Nanog transcriptional activity. , 2014, Biochemical and biophysical research communications.

[5]  Paola Chiarugi,et al.  Anoikis molecular pathways and its role in cancer progression. , 2013, Biochimica et biophysica acta.

[6]  L. Zerbini,et al.  The oncogenic TBX3 is a downstream target and mediator of the TGF-β1 signaling pathway , 2013, Molecular biology of the cell.

[7]  Yang Han,et al.  Increased expression of TBX2 is a novel independent prognostic biomarker of a worse outcome in colorectal cancer patients after curative surgery and a potential therapeutic target , 2013, Medical Oncology.

[8]  G. Pflugfelder,et al.  Dpp signaling inhibits proliferation in the Drosophila wing by Omb-dependent regional control of bantam , 2013, Development.

[9]  N. Negre,et al.  Sin3a acts through a multi-gene module to regulate invasion in Drosophila and human tumors , 2013, Oncogene.

[10]  M. Magnuson,et al.  The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation , 2013, The EMBO journal.

[11]  Eva Külshammer,et al.  The actin cross-linker Filamin/Cheerio mediates tumor malignancy downstream of JNK signaling , 2013, Journal of Cell Science.

[12]  Gilles A. Spoden,et al.  The Transcription Factors TBX2 and TBX3 Interact with Human Papillomavirus 16 (HPV16) L2 and Repress the Long Control Region of HPVs , 2013, Journal of Virology.

[13]  R. Cagan,et al.  Caspase signalling in the absence of apoptosis drives Jnk‐dependent invasion , 2013, EMBO reports.

[14]  H. Richardson,et al.  In Drosophila, RhoGEF2 cooperates with activated Ras in tumorigenesis through a pathway involving Rho1–Rok–Myosin-II and JNK signalling , 2013, Disease Models & Mechanisms.

[15]  G. Mann,et al.  Oncogenic B-RAFV600E signaling induces the T-box3 transcriptional repressor to repress E-cadherin and enhance melanoma cell invasion , 2012, The Journal of investigative dermatology.

[16]  Bin Wang,et al.  The T Box Transcription Factor TBX2 Promotes Epithelial-Mesenchymal Transition and Invasion of Normal and Malignant Breast Epithelial Cells , 2012, PloS one.

[17]  V. Papaioannou,et al.  Diverse functional networks of Tbx3 in development and disease , 2012, Wiley interdisciplinary reviews. Systems biology and medicine.

[18]  V. Mazzaferro,et al.  Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. , 2012, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  A. Dejean,et al.  Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence , 2012, The EMBO journal.

[20]  Ross L Cagan,et al.  Drosophila cancer models , 2012, Developmental dynamics : an official publication of the American Association of Anatomists.

[21]  D. Rimm,et al.  β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. , 2011, Cancer cell.

[22]  G. Gulsen,et al.  TBX3 over-expression causes mammary gland hyperplasia and increases mammary stem-like cells in an inducible transgenic mouse model , 2011, BMC Developmental Biology.

[23]  M. Vidal,et al.  Tumor invasion and metastasis in Drosophila: a bold past, a bright future. , 2011, Journal of genetics and genomics = Yi chuan xue bao.

[24]  G. Morata,et al.  A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila , 2011, Cell Death and Differentiation.

[25]  J. C. Pastor-Pareja,et al.  Shaping cells and organs in Drosophila by opposing roles of fat body-secreted Collagen IV and perlecan. , 2011, Developmental cell.

[26]  G. Mardon,et al.  Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling , 2011, Oncogene.

[27]  Franziska Greulich,et al.  Mechanisms of T-box gene function in the developing heart. , 2011, Cardiovascular research.

[28]  B. Cieply,et al.  A Pathway for the Control of Anoikis Sensitivity by E-Cadherin and Epithelial-to-Mesenchymal Transition , 2011, Molecular and Cellular Biology.

[29]  M. Duman-Scheel,et al.  The Drosophila Netrin receptor frazzled/DCC functions as an invasive tumor suppressor , 2011, BMC Developmental Biology.

[30]  V. Christoffels,et al.  Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43 , 2011, Cellular and Molecular Life Sciences.

[31]  A. Bosserhoff,et al.  Melanoblasts in culture as an in vitro system to determine molecular changes in melanoma , 2011, Experimental dermatology.

[32]  Jessica E. Bolden,et al.  Identification of Novel Ras-Cooperating Oncogenes in Drosophila melanogaster: A RhoGEF/Rho-Family/JNK Pathway Is a Central Driver of Tumorigenesis , 2011, Genetics.

[33]  D. Raben,et al.  Combinatorial effect of maytansinol and radiation in Drosophila and human cancer cells , 2011, Disease Models & Mechanisms.

[34]  P. Fort,et al.  Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling , 2011, The Journal of cell biology.

[35]  A. Bosserhoff,et al.  Post‐transcriptional regulation controlled by E‐cadherin is important for c‐Jun activity in melanoma , 2011, Pigment cell & melanoma research.

[36]  D. Rossell,et al.  Ectopic Expression of Germline Genes Drives Malignant Brain Tumor Growth in Drosophila , 2010, Science.

[37]  E. Lander,et al.  Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling , 2010, Proceedings of the National Academy of Sciences.

[38]  H. Richardson,et al.  Lgl, the SWH pathway and tumorigenesis: It’s a matter of context and competition! , 2010, Cell cycle.

[39]  Juan Lu,et al.  TBX2 and TBX3: The special value for anticancer drug targets , 2010, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.

[40]  Julia B. Cordero,et al.  Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. , 2010, Developmental cell.

[41]  P. Johnston,et al.  T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells , 2010, Oncogene.

[42]  Stuart A. Aaronson,et al.  Drosophila Abelson kinase mediates cell invasion and proliferation via two distinct MAPK pathways , 2010, Oncogene.

[43]  E. Davis,et al.  The Highly Homologous T-Box Transcription Factors, TBX2 and TBX3, Have Distinct Roles in the Oncogenic Process. , 2010, Genes & cancer.

[44]  G. Pflugfelder,et al.  Spatial discontinuity of Optomotor-blind expression in the Drosophila wing imaginal disc disrupts epithelial architecture and promotes cell sorting , 2010, BMC Developmental Biology.

[45]  S. Prince,et al.  The T‐box transcription factor Tbx2: Its role in development and possible implication in cancer , 2009, IUBMB life.

[46]  G. Berx,et al.  Involvement of members of the cadherin superfamily in cancer. , 2009, Cold Spring Harbor perspectives in biology.

[47]  C. Dahmann,et al.  Wingless signaling and the control of cell shape in Drosophila wing imaginal discs. , 2009, Developmental biology.

[48]  H. Richardson,et al.  scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs , 2009, BMC Biology.

[49]  H. Behesti,et al.  Loss of Tbx2 delays optic vesicle invagination leading to small optic cups. , 2009, Developmental biology.

[50]  C. Klämbt,et al.  Modeling glioma growth and invasion in Drosophila melanogaster. , 2009, Neoplasia.

[51]  E. Wagner,et al.  Signal integration by JNK and p38 MAPK pathways in cancer development , 2009, Nature Reviews Cancer.

[52]  Paula D. Bos,et al.  Metastasis: from dissemination to organ-specific colonization , 2009, Nature Reviews Cancer.

[53]  C. Klein,et al.  Parallel progression of primary tumours and metastases , 2009, Nature Reviews Cancer.

[54]  J. C. Pastor-Pareja,et al.  Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. , 2009, Developmental cell.

[55]  A. Gill,et al.  Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas. , 2009, The Journal of clinical endocrinology and metabolism.

[56]  T. Kessler,et al.  Cleavage of Armadillo/beta-catenin by the caspase DrICE in Drosophila apoptotic epithelial cells , 2009, BMC Developmental Biology.

[57]  Bassem A. Hassan,et al.  The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila , 2009, PLoS biology.

[58]  Bassem A. Hassan,et al.  Atonal homolog 1 Is a Tumor Suppressor Gene , 2009, PLoS biology.

[59]  R. Buccione,et al.  Invadopodia: specialized tumor cell structures for the focal degradation of the extracellular matrix , 2009, Cancer and Metastasis Reviews.

[60]  G. Pflugfelder.  omb and circumstance , 2009, Journal of neurogenetics.

[61]  Y. Bellaiche,et al.  Drosophila Cip4 and WASp Define a Branch of the Cdc42-Par6-aPKC Pathway Regulating E-Cadherin Endocytosis , 2008, Current Biology.

[62]  S. Weiss,et al.  Breaching the basement membrane: who, when and how? , 2008, Trends in cell biology.

[63]  L. Lanfrancone,et al.  Tbx3 represses E-cadherin expression and enhances melanoma invasiveness. , 2008, Cancer research.

[64]  H. Varmus,et al.  Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung , 2008, Science.

[65]  A. Wells,et al.  E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas , 2008, Clinical & Experimental Metastasis.

[66]  T. Weil,et al.  Fluorescent core/shell nanoparticles for specific cell-nucleus staining. , 2008, Small.

[67]  A. Moorman,et al.  Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43. , 2008, Cardiovascular research.

[68]  E. Lander,et al.  Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. , 2008, Cancer research.

[69]  B. Degnan,et al.  Genesis and expansion of metazoan transcription factor gene classes. , 2008, Molecular biology and evolution.

[70]  N. Perrimon,et al.  Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes , 2008, Nature Genetics.

[71]  Y. Shintani,et al.  Cadherin switching , 2008, Journal of Cell Science.

[72]  G. Pflugfelder,et al.  optomotor-blind suppresses instability at the A/P compartment boundary of the Drosophila wing , 2008, Mechanisms of Development.

[73]  H. Anton-Culver,et al.  TBX3 is overexpressed in breast cancer and represses p14 ARF by interacting with histone deacetylases. , 2008, Cancer research.

[74]  C. Goding,et al.  UV-mediated Regulation of the Anti-senescence Factor Tbx2* , 2008, Journal of Biological Chemistry.

[75]  R. Eils,et al.  Systemic spread is an early step in breast cancer. , 2008, Cancer cell.

[76]  C. Dahmann,et al.  Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[77]  B. Bilican,et al.  T-box factors: targeting to chromatin and interaction with the histone H3 N-terminal tail. , 2007, Pigment cell research.

[78]  Ken W. Y. Cho,et al.  TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis. , 2007, Genes & development.

[79]  Michelle Starz-Gaiano,et al.  Modeling Migration and Metastasis in Drosophila , 2007, Journal of Mammary Gland Biology and Neoplasia.

[80]  A. Shearn,et al.  Metastatic ability of Drosophila tumors depends on MMP activity. , 2007, Developmental biology.

[81]  J. C. Pastor-Pareja,et al.  Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion , 2007, Proceedings of the National Academy of Sciences.

[82]  S. Cairo,et al.  Tbx3 is a downstream target of the Wnt/beta-catenin pathway and a critical mediator of beta-catenin survival functions in liver cancer. , 2007, Cancer research.

[83]  G. Merlo,et al.  TBX3, the gene mutated in ulnar-mammary syndrome, promotes growth of mammary epithelial cells via repression of p19ARF, independently of p53 , 2007, Cell and Tissue Research.

[84]  D. Bohmann,et al.  JNK‐ and Fos‐regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila , 2006, The EMBO journal.

[85]  D. Alpers.  Faculty Opinions recommendation of The emergence of geometric order in proliferating metazoan epithelia. , 2006 .

[86]  S. Weiss,et al.  A cancer cell metalloprotease triad regulates the basement membrane transmigration program. , 2006, Genes & development.

[87]  T. Igaki,et al.  Loss of Cell Polarity Drives Tumor Growth and Invasion through JNK Activation in Drosophila , 2006, Current Biology.

[88]  R. Cagan,et al.  Drosophila models for cancer research. , 2006, Current opinion in genetics & development.

[89]  J. Bolívar,et al.  Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing , 2006, Nature.

[90]  F. Zindy,et al.  Tbx3, the ulnar‐mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53‐independent pathway , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[91]  Thomas Kirchner,et al.  Migrating cancer stem cells — an integrated concept of malignant tumour progression , 2005, Nature Reviews Cancer.

[92]  H. Richardson,et al.  Using Drosophila melanogaster to map human cancer pathways , 2005, Nature Reviews Cancer.

[93]  S. Noselli,et al.  Dynamics of the basement membrane in invasive epithelial clusters in Drosophila , 2005, Development.

[94]  Keith W. Vance,et al.  Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. , 2005, Cancer research.

[95]  Satoru Takahashi,et al.  Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells. , 2005, Cancer letters.

[96]  H. Simon,et al.  T‐box genes and congenital heart/limb malformations , 2004, Clinical genetics.

[97]  A. Garcı́a-Bellido,et al.  Invasive cell behavior during Drosophila imaginal disc eversion is mediated by the JNK signaling cascade. , 2004, Developmental cell.

[98]  S. Ariyan,et al.  Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. , 2004, Cancer research.

[99]  B. Biehs,et al.  brinker and optomotor-blind act coordinately to initiate development of the L5 wing vein primordium in Drosophila , 2004, Development.

[100]  R. Niles,et al.  T-box binding protein type two (TBX2) is an immediate early gene target in retinoic-acid-treated B16 murine melanoma cells. , 2004, Experimental cell research.

[101]  F. Couch,et al.  The Role of Tbx2 and Tbx3 in Mammary Development and Tumorigenesis , 2004, Journal of Mammary Gland Biology and Neoplasia.

[102]  G. Halder,et al.  Drosophila as an emerging model to study metastasis , 2004, Genome Biology.

[103]  Ronald L. Davis,et al.  Spatiotemporal Rescue of Memory Dysfunction in Drosophila , 2003, Science.

[104]  Tian Xu,et al.  A Genetic Screen in Drosophila for Metastatic Behavior , 2003, Science.

[105]  Erik Sahai,et al.  Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis , 2003, Nature Cell Biology.

[106]  B. Gumbiner,et al.  Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin , 2003, The Journal of cell biology.

[107]  Virginia E. Papaioannou,et al.  Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome , 2003, Development.

[108]  E. A. Packham,et al.  T-box genes in human disorders. , 2003, Human molecular genetics.

[109]  K. Brew,et al.  Protein Engineering of the Tissue Inhibitor of Metalloproteinase 1 (TIMP-1) Inhibitory Domain , 2003, The Journal of Biological Chemistry.

[110]  M. Fraga,et al.  The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors , 2003, Journal of Cell Science.

[111]  R. Fehon,et al.  Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity , 2003, Nature.

[112]  E. Knust,et al.  Composition and Formation of Intercellular Junctions in Epithelial Cells , 2002, Science.

[113]  M. O’Connor,et al.  Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. , 2002, Developmental biology.

[114]  Fergus J Couch,et al.  TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors. , 2002, Cancer research.

[115]  P. Hurlin,et al.  Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation , 2002, Oncogene.

[116]  Z. Werb,et al.  New functions for the matrix metalloproteinases in cancer progression , 2002, Nature Reviews Cancer.

[117]  M. MacDonald,et al.  TBX-3, the Gene Mutated in Ulnar-Mammary Syndrome, Is a Negative Regulator of p19 ARF and Inhibits Senescence* , 2002, The Journal of Biological Chemistry.

[118]  Louise P. Cramer,et al.  An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism , 2001, Current Biology.

[119]  J. Schmitt,et al.  A Murine Model of Holt-Oram Syndrome Defines Roles of the T-Box Transcription Factor Tbx5 in Cardiogenesis and Disease , 2001, Cell.

[120]  G. Berx,et al.  The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. , 2001, Molecular cell.

[121]  Marc J. van de Vijver,et al.  Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers , 2000, Nature Genetics.

[122]  B. Hay,et al.  Understanding IAP function and regulation: a view from Drosophila , 2000, Cell Death and Differentiation.

[123]  J. Kononen,et al.  Multiple genes at 17q23 undergo amplification and overexpression in breast cancer. , 2000, Cancer research.

[124]  M. Mlodzik,et al.  Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye. , 2000, Development.

[125]  T. Godenschwege,et al.  Inflated wings, tissue autolysis and early death in tissue inhibitor of metalloproteinases mutants of Drosophila. , 2000, European journal of cell biology.

[126]  Liqun Luo,et al.  Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis , 1999, Neuron.

[127]  Gerhard Christofori,et al.  A causal role for E-cadherin in the transition from adenoma to carcinoma , 1998, Nature.

[128]  A. Martinez-Arias,et al.  puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. , 1998, Genes & development.

[129]  E. Martín-Blanco.  Regulation of cell differentiation by the Drosophila Jun kinase cascade. , 1997, Current opinion in genetics & development.

[130]  J. Seidman,et al.  Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome , 1997, Nature Genetics.

[131]  S. Zipursky,et al.  Induction of Drosophila eye development by decapentaplegic. , 1997, Development.

[132]  B. Sanson,et al.  Uncoupling cadherin-based adhesion from wingless signalling in Drosophila , 1996, Nature.

[133]  G. Struhl,et al.  Direct and Long-Range Action of a DPP Morphogen Gradient , 1996, Cell.

[134]  G. Pflugfelder,et al.  Control of the Gene optomotor-blind in Drosophila Wing Development by decapentaplegic and wingless , 1996, Science.

[135]  Gerald M. Rubin,et al.  Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death , 1995, Cell.

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

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

[138]  H. Gutzeit,et al.  Laminin and basement membrane-associated microfilaments in wild-type and mutant Drosophila ovarian follicles. , 1991, Journal of cell science.

[139]  C. Goding,et al.  PMA-induced up-regulation of TBX3 is mediated by AP-1 and contributes to breast cancer cell migration. , 2011, The Biochemical journal.

[140]  L. Ylagan,et al.  Tumorigenesis and Neoplastic Progression A Role for the Epithelial Microenvironment at Tumor Boundaries Evidence from Drosophila and Human Squamous Cell Carcinomas , 2010 .

[141]  Raymond E. Moellering,et al.  Direct inhibition of the NOTCH transcription factor complex , 2010, Nature.

[142]  K. Golic,et al.  Methods for homologous recombination in Drosophila. , 2008, Methods in molecular biology.

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

[144]  Ethan Bier,et al.  Drosophila, the golden bug, emerges as a tool for human genetics , 2005, Nature Reviews Genetics.

[145]  E. Lander,et al.  A molecular signature of metastasis in primary solid tumors , 2003, Nature Genetics.

[146]  P. Friedl,et al.  The Journal of Cell Biology , 2002 .

[147]  S. Hanash,et al.  Overexpressed genes/ESTs and characterization of distinct amplicons on 17q23 in breast cancer cells. , 2001, Neoplasia.

[148]  S. Noselli.  JNK signaling and morphogenesis in Drosophila. , 1998, Trends in genetics : TIG.