{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:12:56Z","timestamp":1764936776605,"version":"3.41.2"},"reference-count":53,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>Organ shaping and patterning depends on the coordinated regulation of multiple processes. The Drosophila compound eye provides an excellent model to study the coordination of cell fate and cell positioning during morphogenesis. Here, we find that loss of vav oncogene function during eye development is associated with a disorganised retina characterised by the presence of additional cells of all types. We demonstrate that these defects result from two distinct roles of Vav. First, and in contrast to its well-established role as a positive effector of the EGF receptor (EGFR), we show that readouts of the EGFR pathway are upregulated in vav mutant larval eye disc and pupal retina, indicating that Vav antagonises EGFR signalling during eye development. Accordingly, decreasing EGFR signalling in vav mutant eyes restores retinal organisation and rescues most vav mutant phenotypes. Second, using live imaging in the pupal retina, we observe that vav mutant cells do not form stable adherens junctions, causing various defects, such as recruitment of extra primary pigment cells. In agreement with this role in junction dynamics, we observe that these phenotypes can be exacerbated by lowering DE-Cadherin or Cindr levels. Taken together, our findings establish that Vav acts at multiple times during eye development to prevent excessive cell recruitment by limiting EGFR signalling and by regulating junction dynamics to ensure the correct patterning and morphogenesis of the Drosophila eye.<\/jats:p>","DOI":"10.1242\/dev.110585","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T13:06:45Z","timestamp":1427461605000},"source":"Crossref","is-referenced-by-count":8,"title":["The <i>vav<\/i> oncogene antagonises EGFR signalling and regulates adherens junction dynamics during <i>Drosophila<\/i> eye development"],"prefix":"10.1242","author":[{"given":"Maria-Dolores","family":"Mart\u00edn-Bermudo","sequence":"first","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo CSIC-Univ. Pablo de Olavide, Sevilla 41013, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre-Luc","family":"Bardet","sequence":"additional","affiliation":[{"name":"Institut Curie, CNRS UMR3215, INSERM U934, Paris Cedex 05 75248, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohanns","family":"Bella\u00efche","sequence":"additional","affiliation":[{"name":"Institut Curie, CNRS UMR3215, INSERM U934, Paris Cedex 05 75248, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Malartre","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo CSIC-Univ. Pablo de Olavide, Sevilla 41013, Spain"},{"name":"Universit\u00e9 Paris-Sud, INSERM UMR-S757, Orsay 91405, France"},{"name":"Centre de G\u00e9n\u00e9tique Mol\u00e9culaire\u2008(UPR3404), CNRS, 1 avenue de la Terrasse, Gif-Sur-Yvette 91198, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042608224247900_DEV110585C1","doi-asserted-by":"publisher","first-page":"e1004087","DOI":"10.1371\/journal.pgen.1004087","article-title":"Notch controls cell adhesion in the Drosophila eye","volume":"10","author":"Bao","year":"2014","journal-title":"PLoS Genet."},{"key":"2021042608224247900_DEV110585C2","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.devcel.2005.03.011","article-title":"Preferential adhesion mediated by Hibris and Roughest regulates morphogenesis and patterning in the Drosophila eye","volume":"8","author":"Bao","year":"2005","journal-title":"Dev. Cell"},{"key":"2021042608224247900_DEV110585C3","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.devcel.2013.04.020","article-title":"PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue","volume":"25","author":"Bardet","year":"2013","journal-title":"Dev. Cell"},{"key":"2021042608224247900_DEV110585C4","doi-asserted-by":"publisher","first-page":"R292","DOI":"10.1016\/S0960-9822(01)00167-1","article-title":"Epidermal growth factor receptor signaling","volume":"11","author":"Bogdan","year":"2001","journal-title":"Curr. Biol."},{"key":"2021042608224247900_DEV110585C5","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/0092-8674(94)90362-X","article-title":"A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways","volume":"76","author":"Brunner","year":"1994","journal-title":"Cell"},{"key":"2021042608224247900_DEV110585C6","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1128\/MCB.20.5.1461-1477.2000","article-title":"Regulatory and signaling properties of the Vav family","volume":"20","author":"Bustelo","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2021042608224247900_DEV110585C7","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/356068a0","article-title":"Product of vav proto-oncogene defines a new class of tyrosine protein kinase substrates","volume":"356","author":"Bustelo","year":"1992","journal-title":"Nature"},{"key":"2021042608224247900_DEV110585C8","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S0092-8674(00)80576-0","article-title":"Sprouty, an intracellular inhibitor of Ras signaling","volume":"96","author":"Casci","year":"1999","journal-title":"Cell"},{"key":"2021042608224247900_DEV110585C9","doi-asserted-by":"publisher","first-page":"ra71","DOI":"10.1126\/scisignal.2002962","article-title":"The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells","volume":"5","author":"Citterio","year":"2012","journal-title":"Sci. Signal."},{"key":"2021042608224247900_DEV110585C10","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.yexcr.2005.04.035","article-title":"Phylogenetic conservation of the regulatory and functional properties of the Vav oncoprotein family","volume":"308","author":"Couceiro","year":"2005","journal-title":"Exp. Cell Res."},{"key":"2021042608224247900_DEV110585C11","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.neuron.2005.03.019","article-title":"Vav family GEFs link activated Ephs to endocytosis and axon guidance","volume":"46","author":"Cowan","year":"2005","journal-title":"Neuron"},{"key":"2021042608224247900_DEV110585C12","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0014-5793(00)01413-7","article-title":"Identification of the Drosophila melanogaster homologue of the mammalian signal transducer protein, Vav","volume":"472","author":"Dekel","year":"2000","journal-title":"FEBS Lett."},{"key":"2021042608224247900_DEV110585C13","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ydbio.2004.05.026","article-title":"Regulation of R7 and R8 differentiation by the spalt genes","volume":"273","author":"Domingos","year":"2004","journal-title":"Dev. Biol."},{"key":"2021042608224247900_DEV110585C15","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1242\/jcs.124438","article-title":"GTP exchange factor Vav regulates guided cell migration by coupling guidance receptor signalling to local Rac activation","volume":"126","author":"Fern\u00e1ndez-Espartero","year":"2013","journal-title":"J. Cell Sci."},{"key":"2021042608224247900_DEV110585C16","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1242\/dev.120.8.2297","article-title":"Misexpression of the Drosophila argos gene, a secreted regulator of cell determination","volume":"120","author":"Freeman","year":"1994","journal-title":"Development"},{"key":"2021042608224247900_DEV110585C17","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/S0092-8674(00)81385-9","article-title":"Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye","volume":"87","author":"Freeman","year":"1996","journal-title":"Cell"},{"key":"2021042608224247900_DEV110585C18","doi-asserted-by":"publisher","first-page":"4483","DOI":"10.1242\/dev.00617","article-title":"Mechanism of inhibition of the Drosophila and mammalian EGF receptors by the transmembrane protein Kekkon 1","volume":"130","author":"Ghiglione","year":"2003","journal-title":"Development"},{"key":"2021042608224247900_DEV110585C153","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1534\/genetics.113.160713","article-title":"Highly specific and efficient CRISPR\/Cas9-catalyzed homology-directed repair in Drosophila","volume":"196","author":"Gratz","year":"2014","journal-title":"Genetics"},{"key":"2021042608224247900_DEV110585C20","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1242\/dev.01800","article-title":"IrreC\/rst-mediated cell sorting during Drosophila pupal eye development depends on proper localisation of DE-cadherin","volume":"132","author":"Grzeschik","year":"2005","journal-title":"Development"},{"key":"2021042608224247900_DEV110585C21","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/nature02952","article-title":"Surface mechanics mediate pattern formation in the developing retina","volume":"431","author":"Hayashi","year":"2004","journal-title":"Nature"},{"key":"2021042608224247900_DEV110585C22","doi-asserted-by":"publisher","first-page":"6774","DOI":"10.1038\/sj.onc.1207027","article-title":"DroVav, the Drosophila melanogaster homologue of the mammalian Vav proteins, serves as a signal transducer protein in the Rac and DER pathways","volume":"22","author":"Hornstein","year":"2003","journal-title":"Oncogene"},{"key":"2021042608224247900_DEV110585C23","doi-asserted-by":"publisher","first-page":"8284","DOI":"10.1073\/pnas.0900641106","article-title":"Directed, efficient, and versatile modifications of the Drosophila genome by genomic engineering","volume":"106","author":"Huang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042608224247900_DEV110585C24","doi-asserted-by":"publisher","first-page":"e7008","DOI":"10.1371\/journal.pone.0007008","article-title":"A quantitative method to analyze Drosophila pupal eye patterning","volume":"4","author":"Johnson","year":"2009","journal-title":"PLoS ONE"},{"key":"2021042608224247900_DEV110585C25","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1083\/jcb.200706108","article-title":"The Drosophila CD2AP\/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning","volume":"180","author":"Johnson","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021042608224247900_DEV110585C26","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1101\/gad.10.17.2167","article-title":"Ras1 signaling and transcriptional competence in the R7 cell of Drosophila","volume":"10","author":"Kauffmann","year":"1996","journal-title":"Genes Dev."},{"key":"2021042608224247900_DEV110585C27","doi-asserted-by":"publisher","first-page":"2866","DOI":"10.1109\/TIP.2006.877529","article-title":"Optimal spatial adaptation for patch-based image denoising","volume":"15","author":"Kervrann","year":"2006","journal-title":"IEEE Trans. Image Process"},{"key":"2021042608224247900_DEV110585C28","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/dvdy.23707","article-title":"Building an ommatidium one cell at a time","volume":"241","author":"Kumar","year":"2012","journal-title":"Dev. Dyn."},{"key":"2021042608224247900_DEV110585C29","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.mod.2007.11.007","article-title":"Cellular behavior in the developing Drosophila pupal retina","volume":"125","author":"Larson","year":"2008","journal-title":"Mech. Dev."},{"key":"2021042608224247900_DEV110585C30","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.cellsig.2010.10.022","article-title":"Guanine nucleotide exchange factors for RhoGTPases: good therapeutic targets for cancer therapy?","volume":"23","author":"Lazer","year":"2011","journal-title":"Cell. Signal."},{"key":"2021042608224247900_DEV110585C31","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1523\/JNEUROSCI.1820-09.2010","article-title":"The guanine exchange factor vav controls Axon growth and guidance during Drosophila development","volume":"30","author":"Malartre","year":"2010","journal-title":"J. Neurosci."},{"key":"2021042608224247900_DEV110585C32","doi-asserted-by":"publisher","first-page":"24088","DOI":"10.1074\/jbc.M109.014209","article-title":"B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin","volume":"284","author":"Malhotra","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021042608224247900_DEV110585C33","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1242\/dev.026054","article-title":"Fasciclin 2, the Drosophila orthologue of neural cell-adhesion molecule, inhibits EGF receptor signalling","volume":"136","author":"Mao","year":"2009","journal-title":"Development"},{"key":"2021042608224247900_DEV110585C34","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/356071a0","article-title":"Tyrosine phosphorylation of vav proto-oncogene product containing SH2 domain and transcription factor motifs","volume":"356","author":"Margolis","year":"1992","journal-title":"Nature"},{"key":"2021042608224247900_DEV110585C35","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1242\/dev.02788","article-title":"Combinatorial signaling in the specification of primary pigment cells in the Drosophila eye","volume":"134","author":"Nagaraj","year":"2007","journal-title":"Development"},{"issue":"Suppl. 4","key":"2021042608224247900_DEV110585C36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0959-8049(01)00231-3","article-title":"EGFR and cancer prognosis","volume":"37","author":"Nicholson","year":"2001","journal-title":"Eur. J. Cancer"},{"key":"2021042608224247900_DEV110585C37","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1182\/blood-2011-04-351965","article-title":"CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells","volume":"119","author":"Niiro","year":"2012","journal-title":"Blood"},{"key":"2021042608224247900_DEV110585C38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/S0092-8674(00)00040-4","article-title":"Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila","volume":"102","author":"Nolo","year":"2000","journal-title":"Cell"},{"key":"2021042608224247900_DEV110585C39","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1093\/bioinformatics\/btp184","article-title":"Globally optimal stitching of tiled 3D microscopic image acquisitions","volume":"25","author":"Preibisch","year":"2009","journal-title":"Bioinformatics"},{"key":"2021042608224247900_DEV110585C40","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.cub.2007.06.048","article-title":"Antagonistic roles of Rac and Rho in organizing the germ cell microenvironment","volume":"17","author":"Sarkar","year":"2007","journal-title":"Curr. Biol."},{"key":"2021042608224247900_DEV110585C41","doi-asserted-by":"publisher","first-page":"ra83","DOI":"10.1126\/scisignal.2000420","article-title":"Function of the nucleotide exchange activity of vav1 in T cell development and activation","volume":"2","author":"Saveliev","year":"2009","journal-title":"Sci. Signal."},{"key":"2021042608224247900_DEV110585C42","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/S0014-4827(02)00094-0","article-title":"Signaling by the Drosophila epidermal growth factor receptor pathway during development","volume":"284","author":"Shilo","year":"2003","journal-title":"Exp. Cell Res."},{"key":"2021042608224247900_DEV110585C43","doi-asserted-by":"publisher","first-page":"4017","DOI":"10.1242\/dev.02006","article-title":"Regulating the dynamics of EGF receptor signaling in space and time","volume":"132","author":"Shilo","year":"2005","journal-title":"Development"},{"key":"2021042608224247900_DEV110585C44","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/S0960-9822(03)00545-1","article-title":"EGF signaling and ommatidial rotation in the Drosophila eye","volume":"13","author":"Strutt","year":"2003","journal-title":"Curr. Biol."},{"key":"2021042608224247900_DEV110585C45","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrm3802","article-title":"Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling","volume":"15","author":"Takeichi","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042608224247900_DEV110585C46","doi-asserted-by":"publisher","first-page":"5163","DOI":"10.1074\/jbc.M207555200","article-title":"Mechanism of epidermal growth factor regulation of Vav2, a guanine nucleotide exchange factor for Rac","volume":"278","author":"Tam\u00e1s","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021042608224247900_DEV110585C119","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/sj.onc.1206116","article-title":"RhoG regulates gene expression and the actin cytoskeleton in lymphocytes","volume":"22","author":"Vigorito","year":"2003","journal-title":"Oncogene"},{"key":"2021042608224247900_DEV110585C47","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1038\/nprot.2006.379","article-title":"Immunofluorescent staining and imaging of the pupal and adult Drosophila visual system","volume":"1","author":"Walther","year":"2007","journal-title":"Nat. Protoc."},{"key":"2021042608224247900_DEV110585C48","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1083\/jcb.200901029","article-title":"Distinct functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia","volume":"185","author":"Warner","year":"2009","journal-title":"J. Cell Biol."},{"key":"2021042608224247900_DEV110585C49","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1083\/jcb.200906047","article-title":"Cdc42 antagonizes Rho1 activity at adherens junctions to limit epithelial cell apical tension","volume":"187","author":"Warner","year":"2009","journal-title":"J. Cell Biol."},{"key":"2021042608224247900_DEV110585C115","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1242\/dev.117.4.1223","article-title":"Analysis of genetic mosaics in developing and adult Drosophila tissues","volume":"117","author":"Xu","year":"1993","journal-title":"Development"},{"key":"2021042608224247900_DEV110585C51","doi-asserted-by":"publisher","first-page":"2956","DOI":"10.1091\/mbc.E14-04-0894","article-title":"Rho1 regulates adherens junction remodeling by promoting recycling endosome formation through activation of myosin II","volume":"25","author":"Yashiro","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"2021042608224247900_DEV110585C52","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1038\/emboj.2008.58","article-title":"Drosophila EGFR signalling is modulated by differential compartmentalization of Rhomboid intramembrane proteases","volume":"27","author":"Yogev","year":"2008","journal-title":"EMBO J."},{"key":"2021042608224247900_DEV110585C53","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.ymeth.2014.03.020","article-title":"A simple TALEN-based protocol for efficient genome-editing in Drosophila","volume":"69","author":"Zhang","year":"2014","journal-title":"Methods"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/142\/8\/1492\/1842042\/dev110585.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.110585\/2003536\/dev_110585v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.110585\/2003536\/dev_110585v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T21:30:58Z","timestamp":1621373458000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/doi\/10.1242\/dev.110585\/258645\/The-vav-oncogene-antagonises-EGFR-signalling-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,1]]},"references-count":53,"URL":"https:\/\/doi.org\/10.1242\/dev.110585","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"type":"electronic","value":"1477-9129"},{"type":"print","value":"0950-1991"}],"subject":[],"published":{"date-parts":[[2015,1,1]]},"article-number":"dev.110585"}}