title: Laminin alpha5 is essential for the formation of the zebrafish fins.
abstract: The vertebrate fin fold, the presumptive evolutionary antecedent of the paired fins, consists of two layers of epidermal cells extending dorsally and ventrally over the trunk and tail of the embryo, facilitating swimming during the embryonic and larval stages. Development of the fin fold requires dramatic changes in cell shape and adhesion during early development, but the proteins involved in this process are completely unknown. In a screen of mutants defective in fin fold morphogenesis, we identified a mutant with a severe fin fold defect, which also displays malformed pectoral fins. We find that the cause of the defect is a non-sense mutation in the zebrafish lama5 gene that truncates laminin alpha5 before the C-terminal laminin LG domains, thereby preventing laminin alpha5 from interacting with its cell surface receptors. Laminin is mislocalized in this mutant, as are the membrane-associated proteins, actin and beta-catenin, that normally form foci within the fin fold. Ultrastructural analysis revealed severe morphological abnormalities and defects in cell-cell adhesion within the epidermis of the developing fin fold at 36 hpf, resulting in an epidermal sheet that can not extend away from the body. Examining the pectoral fins, we find that the lama5 mutant is the first zebrafish mutant identified in which the pectoral fins fail to make the transition from an apical epidermal ridge to an apical fold, a transformation that is essential for pectoral fin morphogenesis. We propose that laminin alpha5, which is concentrated at the distal ends of the fins, organizes the distal cells of the fin fold and pectoral fins in order to promote the morphogenesis of the epidermis. The lama5 mutant provides novel insight into the role of laminins in the zebrafish epidermis, and the molecular mechanisms driving fin formation in vertebrates.
authors.affiliation: Department of Biochemistry, University of Washington, Box 357350, Seattle, WA 98195-7350, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Webb
authors.forename: Justyn
authors.initials: J
authors.lastname: Sanderford
authors.forename: Diane
authors.initials: D
authors.lastname: Frank
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Driever
authors.forename: David
authors.initials: D
authors.lastname: Kimelman
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D002448:Cell Adhesion / Q000502:physiology; D004252:DNA Mutational Analysis; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology* / Q000254:growth & development; D017403:In Situ Hybridization; D007365:Intercellular Junctions / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007797:Laminin; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; C097043:laminin alpha5