title: The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development.
abstract: 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.
authors: Centro Andaluz de Biología del Desarrollo CSIC-Univ. Pablo de Olavide, Sevilla 41013, Spain.
authors: Maria-Dolores
authors: MD
authors: Martín-Bermudo
authors: Institut Curie, CNRS UMR3215, INSERM U934, Paris Cedex 05 75248, France.
authors: Pierre-Luc
authors: PL
authors: Bardet
authors: Institut Curie, CNRS UMR3215, INSERM U934, Paris Cedex 05 75248, France.
authors: Yohanns
authors: Y
authors: Bellaïche
authors: Centro Andaluz de Biología del Desarrollo CSIC-Univ. Pablo de Olavide, Sevilla 41013, Spain Université Paris-Sud, INSERM UMR-S757, Orsay 91405, France Centre de Génétique Moléculaire (UPR3404), CNRS, 1 avenue de la Terrasse, Gif-Sur-Yvette 91198, France marianne.malartre@u-psud.fr.
authors: Marianne
authors: M
authors: Malartre
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D015820:Cadherins; C528411:Cindr protein, Drosophila; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D051567:Proto-Oncogene Proteins c-vav; C501889:shg protein, Drosophila; D066246:ErbB Receptors
keywords: Adherens junctions; EGFR; Eye patterning; Morphogenesis; Vav