title: miR-204 targeting of Ankrd13A controls both mesenchymal neural crest and lens cell migration.
abstract: Loss of cell adhesion and enhancement of cell motility contribute to epithelial-to-mesenchymal transition during development. These processes are related to a) rearrangement of cell-cell and cell-substrate adhesion molecules; b) cross talk between extra-cellular matrix and internal cytoskeleton through focal adhesion molecules. Focal adhesions are stringently regulated transient structures implicated in cell adhesion, spreading and motility during tissue development. Importantly, despite the extensive elucidation of the molecular composition of focal adhesions, the complex regulation of their dynamics is largely unclear. Here, we demonstrate, using live-imaging in medaka, that the microRNA miR-204 promotes both mesenchymal neural crest and lens cell migration and elongation. Overexpression of miR-204 results in upregulated cell motility, while morpholino-mediated ablation of miR-204 activity causes abnormal lens morphogenesis and neural crest cell mislocalization. Using a variety of in vivo and in vitro approaches, we demonstrate that these actions are mediated by the direct targeting of the Ankrd13A gene, which in turn controls focal cell adhesion formation and distribution. Significantly, in vivo restoration of abnormally elevated levels of Ankrd13A resulting from miR-204 inactivation rescued the aberrant lens phenotype in medaka fish. These data uncover, for the first time in vivo, the role of a microRNA in developmental control of mesenchymal cell migration and highlight miR-204 as a "master regulator" of the molecular networks that regulate lens morphogenesis in vertebrates.
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Avellino
authors.forename: Sabrina
authors.initials: S
authors.lastname: Carrella
authors.forename: Marinella
authors.initials: M
authors.lastname: Pirozzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Risolino
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Salierno
authors.forename: Paola
authors.initials: P
authors.lastname: Franco
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoppelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Verde
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Ivan
authors.initials: I
authors.lastname: Conte
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology*; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D009990:Oryzias / Q000378:metabolism*; D010641:Phenotype
chemical_list: C584194:ANKRD13A protein, human; C549404:MIRN204 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D060172:Morpholinos