Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration

E. Butí, D. Mesquita, S.J. Araújo

Research output: Contribution to journalArticle

7 Citations (Scopus)
1 Downloads (Pure)

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. © 2014 Butí et al.
Original languageEnglish
JournalPLoS ONE
Volume9
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • bnl protein
  • cell protein
  • fibroblast growth factor
  • protein Patched
  • sonic hedgehog protein
  • unclassified drug
  • animal tissue
  • article
  • bnl gene
  • cell activity
  • cell fate
  • cell level
  • cell migration
  • controlled study
  • Drosophila melanogaster
  • embryo
  • embryo cell
  • gene
  • gene expression
  • gene function
  • gene identification
  • genetic transcription
  • molecular dynamics
  • nerve cell
  • nonhuman
  • protein determination
  • protein expression
  • protein function
  • signal transduction
  • Animals
  • Cell Movement
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Epistasis, Genetic
  • Fibroblast Growth Factors
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Models, Biological
  • Morphogenesis
  • Mutation
  • Phenotype
  • Receptors, Cell Surface
  • Signal Transduction
  • Trachea
  • Transcription Factors
  • Transcription, Genetic

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