Laminin β1 and γ1 Containing Laminins Are Essential for Basement Membrane Integrity in the Zebrafish Eye

Abstract

PURPOSE: In this study recessive zebrafish mutations in the genes encoding laminin beta1 (lamb1) and laminin gamma1 (lamc1) were used to determine the functions of these laminin proteins during ocular basement membrane formation and during zebrafish eye development. METHODS: Ocular defects in lamb1 and lamc1 mutants were characterized by using a combination of histology, immunohistochemistry, in situ hybridization, and transmission electron microscopy. RESULTS: The results demonstrated that zebrafish lamb1 and lamc1 mutants possess defects in two ocular basement membranes--the lens capsule and the inner limiting membrane--whereas Bruch's membrane is largely unaffected. lamb1 and lamc1 mutants possess severe lens dysplasias that result from a compromise in lens capsule integrity. Inner limiting membrane continuity is irregular in these mutants, and these irregularities result in small retinal ectopias that extend from the retina into the interstitial space between the retina and the lens. At late embryonic stages (e.g., 5-7 days after fertilization), retinal lamination defects are also observed in a subset of laminin mutants. CONCLUSIONS: The results demonstrate that laminin beta1 and -gamma1 containing laminins are essential for the integrity of the lens capsule basement membrane and inner limiting membrane in the zebrafish eye.