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Heartbroken is a specific downstream mediator of FGF receptor signalling in Drosophila.

Drosophila possesses two FGF receptors which are encoded by the heartless and breathless genes. HEARTLESS is essential for early migration and patterning of the embryonic mesoderm, while BREATHLESS is required for proper branching of the tracheal system. We have identified a new gene, heartbroken, that participates in the signalling pathways of both FGF receptors. Mutations in heartbroken are associated with defects in the migration and later specification of mesodermal and tracheal cells. Genetic interaction and epistasis experiments indicate that heartbroken acts downstream of the two FGF receptors but either upstream of or parallel to RAS1. Furthermore, heartbroken is involved in both the HEARTLESS- and BREATHLESS-dependent activation of MAPK. In contrast, EGF receptor-dependent embryonic functions and MAPK activation are not perturbed in heartbroken mutant embryos. A strong heartbroken allele also suppresses the effects of hyperactivated FGF but not EGF receptors. Thus, heartbroken may contribute to the specificity of developmental responses elicited by FGF receptor signalling.

Pubmed ID: 9778498


  • Michelson AM
  • Gisselbrecht S
  • Buff E
  • Skeath JB


Development (Cambridge, England)

Publication Data

November 19, 1998

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01-NS36570

Mesh Terms

  • Animals
  • Body Patterning
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Movement
  • Drosophila
  • Drosophila Proteins
  • Enzyme Activation
  • Genes, Insect
  • Mesoderm
  • Models, Biological
  • Phenotype
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Receptor, Epidermal Growth Factor
  • Receptors, Fibroblast Growth Factor
  • Receptors, Invertebrate Peptide
  • Signal Transduction
  • Suppression, Genetic
  • Trachea
  • ras Proteins