title: The fat-like gene of Drosophila is the true orthologue of vertebrate fat cadherins and is involved in the formation of tubular organs.
abstract: Fat cadherins constitute a subclass of the large cadherin family characterized by the presence of 34 cadherin motifs. To date, three mammalian Fat cadherins have been described; however, only limited information is known about the function of these molecules. In this paper, we describe the second fat cadherin in Drosophila, fat-like (ftl). We show that ftl is the true orthologue of vertebrate fat-like genes, whereas the previously characterized tumor suppressor cadherin, fat, is more distantly related as compared with ftl. Ftl is a large molecule of 4705 amino acids. It is expressed apically in luminal tissues such as trachea, salivary glands, proventriculus, and hindgut. Silencing of ftl results in the collapse of tracheal epithelia giving rise to breaks, deletions, and sac-like structures. Other tubular organs such as proventriculus, salivary glands, and hindgut are also malformed or missing. These data suggest that Ftl is required for morphogenesis and maintenance of tubular structures of ectodermal origin and underline its similarity in function to a reported lethal mouse knock-out of fat1 where glomerular epithelial processes collapse. Based on our results, we propose a model where Ftl acts as a spacer to keep tubular epithelia apart rather than the previously described adhesive properties of the cadherin superfamily.
authors.affiliation: Department of Cell and Molecular Biology, Lund University, BMC B13, S-22184 Lund, Sweden. Casimiro.Castillejo-Lopez@medkem.lu.se
authors.forename: Casimiro
authors.initials: C
authors.lastname: Castillejo-López
authors.forename: Wilma Martinez
authors.initials: WM
authors.lastname: Arias
authors.forename: Stefan
authors.initials: S
authors.lastname: Baumgartner
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics*; D002448:Cell Adhesion; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D004475:Ectoderm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D017403:In Situ Hybridization; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D019076:Transgenes
chemical_list: D000906:Antibodies; D015820:Cadherins; C502406:fat1 protein, mouse