title: Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration.
abstract: Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration.
authors.affiliation: Developmental Biology Department, Institute of Molecular Biology of Barcelona (IBMB-CSIC), Barcelona, Spain; Cell and Developmental Biology Programme, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Butí
authors.affiliation: Developmental Biology Department, Institute of Molecular Biology of Barcelona (IBMB-CSIC), Barcelona, Spain; Cell and Developmental Biology Programme, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Duarte
authors.initials: D
authors.lastname: Mesquita
authors.affiliation: Developmental Biology Department, Institute of Molecular Biology of Barcelona (IBMB-CSIC), Barcelona, Spain; Cell and Developmental Biology Programme, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Sofia J
authors.initials: SJ
authors.lastname: Araújo
mesh_terms: D000818:Animals; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D004843:Epistasis, Genetic; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014132:Trachea / Q000166:cytology* / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C102644:bnl protein, Drosophila; C070844:ptc protein, Drosophila; C096359:sr protein, Drosophila; D005346:Fibroblast Growth Factors