title: Ectopic expression screen identifies genes affecting Drosophila mesoderm development including the HSPG Trol.
abstract: Gastrulation of the embryo involves coordinate cell movements likely supported by multiple signaling pathways, adhesion molecules, and extracellular matrix components. Fibroblast growth factors (FGFs) have a major role in Drosophila melanogaster mesoderm migration; however, few other inputs are known and the mechanism supporting cell movement is unclear. To provide insight, we performed an ectopic expression screen to identify secreted or membrane-associated molecules that act to support mesoderm migration. Twenty-four UAS insertions were identified that cause lethality when expressed in either the mesoderm (Twi-Gal4) or the ectoderm (69B-Gal4). The list was narrowed to a subset of 10 genes that were shown to exhibit loss-of-function mutant phenotypes specifically affecting mesoderm migration. These include the FGF ligand Pyramus, α-integrins, E-cadherin, Cueball, EGFR, JAK/STAT signaling components, as well as the heparan sulfate proteoglycan (HSPG) Terribly reduced optic lobes (Trol). Trol encodes the ortholog of mammalian HSPG Perlecan, a demonstrated FGF signaling cofactor. Here, we examine the role of Trol in Drosophila mesoderm migration and compare and contrast its role with that of Syndecan (Sdc), another HSPG previously implicated in this process. Embryos mutant for Trol or Sdc were obtained and analyzed. Our data support the view that both HSPGs function to support FGF-dependent processes in the early embryo as they share phenotypes with FGF mutants: Trol in terms of effects on mesoderm migration and caudal visceral mesoderm (CVM) migration and Sdc in terms of dorsal mesoderm specification. The differential roles uncovered for these two HSPGs suggest that HSPG cofactor choice may modify FGF-signaling outputs.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, MC 114-96, Pasadena, California 91125.
authors.forename: Nathanie
authors.initials: N
authors.lastname: Trisnadi
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, MC 114-96, Pasadena, California 91125 angelike@caltech.edu.
authors.forename: Angelike
authors.initials: A
authors.lastname: Stathopoulos
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D004625:Embryo, Nonmammalian; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics*; D008297:Male; D008648:Mesoderm / Q000254:growth & development*; D053667:Syndecans / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D019812:Heparan Sulfate Proteoglycans; D053667:Syndecans; C472788:trol protein, Drosophila
keywords: Drosophila; Trol Syndecan; embryogenesis; fibroblast growth factors; heparan sulfate proteoglycan; mesoderm cell migration