title: ojoplano-mediated basal constriction is essential for optic cup morphogenesis.
abstract: Although the vertebrate retina is a well-studied paradigm for organogenesis, the morphogenetic mechanisms that carve the architecture of the vertebrate optic cup remain largely unknown. Understanding how the hemispheric shape of an eye is formed requires addressing the fundamental problem of how individual cell behaviour is coordinated to direct epithelial morphogenesis. Here, we analyze the role of ojoplano (opo), an uncharacterized gene whose human ortholog is associated with orofacial clefting syndrome, in the morphogenesis of epithelial tissues. Most notably, when opo is mutated in medaka fish, optic cup folding is impaired. We characterize optic cup morphogenesis in vivo and determine at the cellular level how opo affects this process. opo encodes a developmentally regulated transmembrane protein that localizes to compartments of the secretory pathway and to basal end-feet of the neuroepithelial precursors. We show that Opo regulates the polarized localization of focal adhesion components to the basal cell surface. Furthermore, tissue-specific interference with integrin-adhesive function impairs optic cup folding, resembling the ocular phenotype observed in opo mutants. We propose a model of retinal morphogenesis whereby opo-mediated formation of focal contacts is required to transmit the mechanical tensions that drive the macroscopic folding of the vertebrate optic cup.
authors.affiliation: Developmental unit, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. jrmarmor@upo.es
authors.forename: Juan Ramon
authors.initials: JR
authors.lastname: Martinez-Morales
authors.forename: Martina
authors.initials: M
authors.lastname: Rembold
authors.forename: Klaus
authors.initials: K
authors.lastname: Greger
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Brown
authors.forename: Rebecca
authors.initials: R
authors.lastname: Quiring
authors.forename: Rainer
authors.initials: R
authors.lastname: Pepperkok
authors.forename: Maria D
authors.initials: MD
authors.lastname: Martin-Bermudo
authors.forename: Heinz
authors.initials: H
authors.lastname: Himmelbauer
authors.forename: Joachim
authors.initials: J
authors.lastname: Wittbrodt
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D004252:DNA Mutational Analysis; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005123:Eye / Q000033:anatomy & histology / Q000196:embryology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D009958:Orofaciodigital Syndromes / Q000235:genetics; D009990:Oryzias / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D029941:Fish Proteins; D016023:Integrins; D008565:Membrane Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins