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.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA. michelson@rascal.med.harvard.edu
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D000818:Animals; D019521:Body Patterning / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002465:Cell Movement; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D017344:Genes, Insect; D008648:Mesoderm; D008954:Models, Biological; D010641:Phenotype; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism; D015398:Signal Transduction; D013489:Suppression, Genetic; D014132:Trachea / Q000196:embryology; D018631:ras Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D017468:Receptors, Fibroblast Growth Factor; D018010:Receptors, Invertebrate Peptide; D011494:Protein Kinases; C102301:BTL protein, Drosophila; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C102667:htl protein, Drosophila; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins