title: Nemo regulates cell dynamics and represses the expression of miple, a midkine/pleiotrophin cytokine, during ommatidial rotation.
abstract: Ommatidial rotation is one of the most important events for correct patterning of the Drosophila eye. Although several signaling pathways are involved in this process, few genes have been shown to specifically affect it. One of them is nemo (nmo), which encodes a MAP-like protein kinase that regulates the rate of rotation throughout the entire process, and serves as a link between core planar cell polarity (PCP) factors and the E-cadherin-β-catenin complex. To determine more precisely the role of nmo in ommatidial rotation, live-imaging analyses in nmo mutant and wild-type early pupal eye discs were performed. We demonstrate that ommatidial rotation is not a continuous process, and that rotating and non-rotating interommatidial cells are very dynamic. Our in vivo analyses also show that nmo regulates the speed of rotation and is required in cone cells for correct ommatidial rotation, and that these cells as well as interommatidial cells are less dynamic in nmo mutants. Furthermore, microarray analyses of nmo and wild-type larval eye discs led us to identify new genes and signaling pathways related to nmo function during this process. One of them, miple, encodes the Drosophila ortholog of the midkine/pleiotrophin secreted cytokines that are involved in cell migration processes. miple is highly up-regulated in nmo mutant discs. Indeed, phenotypic analyses reveal that miple overexpression leads to ommatidial rotation defects. Genetic interaction assays suggest that miple is signaling through Ptp99A, the Drosophila ortholog of the vertebrate midkine/pleiotrophin PTPζ receptor. Accordingly, we propose that one of the roles of Nmo during ommatial rotation is to repress miple expression, which may in turn affect the dynamics in E-cadherin-β-catenin complexes.
authors: Departamento de Genética, Facultad de CC Biológicas, Universidad de Valencia, Doctor Moliner 50, E-46100 Burjassot, Valencia, Spain.
authors: Verónica
authors: V
authors: Muñoz-Soriano
authors: Carlos
authors: C
authors: Ruiz
authors: Manuel
authors: M
authors: Pérez-Alonso
authors: Marek
authors: M
authors: Mlodzik
authors: Nuria
authors: N
authors: Paricio
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D015820:Cadherins / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000648:ultrastructure; D005123:Eye / Q000033:anatomy & histology* / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D060227:Imaginal Discs / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D021621:Imaging, Three-Dimensional; D000078792:Midkine; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012399:Rotation; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D016207:Cytokines; D029721:Drosophila Proteins; C514347:Miple1 protein, Drosophila; D051176:beta Catenin; D000078792:Midkine; D020928:Mitogen-Activated Protein Kinases; C110707:nmo protein, Drosophila