Elsevier

Developmental Biology

Volume 299, Issue 1, 1 November 2006, Pages 63-77
Developmental Biology

Mutations in laminin alpha 1 result in complex, lens-independent ocular phenotypes in zebrafish

https://doi.org/10.1016/j.ydbio.2006.07.005Get rights and content
Under an Elsevier user license
open archive

Abstract

We report phenotypic and genetic analyses of a recessive, larval lethal zebrafish mutant, bala69, characterized by severe eye defects and shortened body axis. The bala69 mutation was mapped to chromosome 24 near the laminin alpha 1 (lama1) gene. We analyzed the lama1 gene sequence within bala69 embryos and two allelic mutants, balarl and baluw1. Missense (bala69), nonsense (balarl), and frameshift (baluw1) alterations in lama1 were found to underlie the phenotypes. Extended analysis of bala69 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, bala69 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 bala69 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.

Keywords

Basement membrane
Focal adhesion kinase
Cornea
Anterior segment disease
Glaucoma
Cataract
Retinal development

Cited by (0)