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First published online June 5, 2009
doi: 10.1242/10.1242/dev.033563

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ojoplano-mediated basal constriction is essential for optic cup morphogenesis

Juan Ramon Martinez-Morales^1,2,*, Martina Rembold¹, Klaus Greger³, Jeremy C. Simpson³, Katherine E. Brown¹, Rebecca Quiring¹, Rainer Pepperkok³, Maria D. Martin-Bermudo², Heinz Himmelbauer^4, and Joachim Wittbrodt^1,,*

¹ Developmental unit, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
² Centro Andaluz de Biología del Desarrollo (UPO/CSIC), 41013 Sevilla, Spain.
³ Cell Biology unit, EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
⁴ Max-Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin-Dahlem, Germany.

^* Authors for correspondence (e-mails: jrmarmor{at}upo.es; Jochen.Wittbrodt{at}EMBL-Heidelberg.de)

Accepted 22 April 2009

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.

Key words: Medaka fish, Optic cup, Organogenesis

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