RRC ID 30226
Author Martinez-Morales JR, Rembold M, Greger K, Simpson JC, Brown KE, Quiring R, Pepperkok R, Martin-Bermudo MD, Himmelbauer H, Wittbrodt J.
Title ojoplano-mediated basal constriction is essential for optic cup morphogenesis.
Journal Development
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.
Volume 136(13)
Pages 2165-75
Published 2009-7
DOI 10.1242/dev.033563
PII 136/13/2165
PMID 19502481
MeSH Animals Animals, Genetically Modified Base Sequence Cell Nucleus / metabolism DNA Mutational Analysis Epithelium / embryology Epithelium / metabolism Eye / anatomy & histology Eye / embryology* Eye Proteins / genetics Eye Proteins / metabolism* Fish Proteins / genetics Fish Proteins / metabolism* Focal Adhesions / metabolism Humans Integrins / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism* Molecular Sequence Data Morphogenesis / physiology* Orofaciodigital Syndromes / genetics Oryzias / anatomy & histology Oryzias / embryology Oryzias / genetics Oryzias / metabolism Protein Isoforms / genetics Protein Isoforms / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Retina / cytology Retina / metabolism
IF 5.413
Times Cited 36
Medaka Ojoplano (MT934) Cab Kaga