Integrin α5/fibronectin1 and focal adhesion kinase are required for lens fiber morphogenesis in zebrafish. Mol Biol Cell 2012 Dec;23(24):4725-38
Date
10/26/2012Pubmed ID
23097490Pubmed Central ID
PMC3521681DOI
10.1091/mbc.E12-09-0672Scopus ID
2-s2.0-84871191358 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
Lens fiber formation and morphogenesis requires a precise orchestration of cell- extracellular matrix (ECM) and cell-cell adhesive changes in order for a lens epithelial cell to adopt a lens fiber fate, morphology, and migratory ability. The cell-ECM interactions that mediate these processes are largely unknown, and here we demonstrate that fibronectin1 (Fn1), an ECM component, and integrin α5, its cellular binding partner, are required in the zebrafish lens for fiber morphogenesis. Mutations compromising either of these proteins lead to cataracts, characterized by defects in fiber adhesion, elongation, and packing. Loss of integrin α5/Fn1 does not affect the fate or viability of lens epithelial cells, nor does it affect the expression of differentiation markers expressed in lens fibers, although nucleus degradation is compromised. Analysis of the intracellular mediators of integrin α5/Fn1 activity focal adhesion kinase (FAK) and integrin-linked kinase (ILK) reveals that FAK, but not ILK, is also required for lens fiber morphogenesis. These results support a model in which lens fiber cells use integrin α5 to migrate along a Fn-containing substrate on the apical side of the lens epithelium and on the posterior lens capsule, likely activating an intracellular signaling cascade mediated by FAK in order to orchestrate the cytoskeletal changes in lens fibers that facilitate elongation, migration, and compaction.
Author List
Hayes JM, Hartsock A, Clark BS, Napier HR, Link BA, Gross JMAuthor
Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Genetically Modified
Embryo, Nonmammalian
Fibronectins
Focal Adhesion Kinase 1
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Immunohistochemistry
In Situ Hybridization
Integrin alpha5
Lens, Crystalline
Luminescent Proteins
Microscopy, Confocal
Microscopy, Electron
Models, Genetic
Morphogenesis
Mutation
Zebrafish
Zebrafish Proteins
