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Mutations in laminin alpha 1 result in complex, lens-independent ocular phenotypes in zebrafish. Dev Biol 2006 Nov 01;299(1):63-77



Pubmed ID




Scopus ID

2-s2.0-33749507648   49 Citations


We report phenotypic and genetic analyses of a recessive, larval lethal zebrafish mutant, bal(a69), characterized by severe eye defects and shortened body axis. The bal(a69) mutation was mapped to chromosome 24 near the laminin alpha 1 (lama1) gene. We analyzed the lama1 gene sequence within bal(a69) embryos and two allelic mutants, bal(arl) and bal(uw1). Missense (bal(a69)), nonsense (bal(arl)), and frameshift (bal(uw1)) alterations in lama1 were found to underlie the phenotypes. Extended analysis of bal(a69) ocular features revealed disrupted lens development with subsequent lens degeneration, focal cornea dysplasia, and hyaloid vasculature defects. Within the neural retina, the ganglion cells showed axonal projection defects and ectopic photoreceptor cells were noted at inner retinal locations. To address whether ocular anomalies were secondary to defects in lens differentiation, bal(a69) mutants were compared to embryos in which the lens vesicle was surgically removed. Our analysis suggests that many of the anterior and posterior ocular defects in bal(a69) are independent of the lens degeneration. Analysis of components of focal adhesion signaling complexes suggests that reduced focal adhesion kinase activation underlies the anterior segment dysgenesis in lama1 mutants. To assess adult ocular phenotypes associated with lama1 mutations, genetic mosaics were generated by transplanting labeled bal cells into ocular-fated regions of wild-type blastulas. Adult chimeric eyes displayed a range of defects including anterior segment dysgenesis and cataracts. Our analysis provides mechanistic insights into the developmental defects and ocular pathogenesis caused by mutations in laminin subunits.

Author List

Semina EV, Bosenko DV, Zinkevich NC, Soules KA, Hyde DR, Vihtelic TS, Willer GB, Gregg RG, Link BA


Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Elena V. Semina PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Anterior Eye Segment
Base Sequence
Cloning, Molecular
DNA Mutational Analysis
Embryo, Nonmammalian
Focal Adhesions
Gene Expression Regulation, Developmental
Lens, Crystalline
Molecular Sequence Data
RNA, Messenger
Retinal Ganglion Cells
Retinal Vessels
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0