Abstract
Abstract: :
Purpose: Laminins constitute a major component of all basal laminae and consist of three polypeptide subunits (laminin alpha, beta and gamma). Laminin heterotrimers are expressed from the early stages of embryogenesis onward in nearly every tissue and are thought to be involved in a variety of developmental processes. While laminin beta 1 (lamb1) and laminin gamma 1 (lamc1) knockout mice have been generated, later in vivo developmental roles for these laminins have been difficult to study, as the knockouts result in early postimplantation lethality. Here we describe alleles of zebrafish lamb1 and lamc1 mutants isolated in a retroviral insertional mutagenesis screen. Methods: Owing to a maternal contribution of mRNA and protein, these zebrafish mutants survive until relatively late in embryogenesis enabling studies of their roles during eye development. Histological, molecular and electron microscopic characterization of these mutants have been performed from 1 day post fertilization (dpf) to 7dpf. Results: Among other morphological phenotypes, these laminin mutants show clear defects in lens and retina development. Mutation of either laminin subunit results in lens hypoplasia, lens capsule rupture and as a result, a dysplastic, free floating lens localized within the retinal neuroepithelium. Both lamb1 and lamc1 mutants also frequently show retinal coloboma with retinal tissue expelling through the retinal pigment epithelium and into the forebrain. Optic nerves appear disorganized in these mutants and photoreceptor outer segment formation is also frequently abnormal. Conclusions: lamb1 and lamc1 are essential for vertebrate lens maintenance, retinal development and retinal containment.
Keywords: extracellular matrix • retinal development