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Gene Review

btl  -  breathless

Drosophila melanogaster

Synonyms: 0844/01, BTL/FGFR2, Btl, CG32134, CG6714, ...
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High impact information on btl

  • In wild-type embryos, the Branchless FGF induces secondary branching by activating the Breathless FGF receptor near the tips of growing primary branches [1].
  • Consistent with this, Btl-GFP chimera expressed from a cognate btl promoter-driven system accumulate at high levels on tracheal cell membrane of awd mutants as well as in awd RNA duplex-treated cultured cells [2].
  • Signal transduction through the FGF receptor is essential for the specification of the vertebrate body plan [3].
  • Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system [4].
  • We have investigated whether the Drosophila FGF receptor homolog, Breathless (BTL), whose activity is necessary for each phase of branching morphogenesis in the embryonic tracheal system, might play a role in guiding the directed migration of tracheal cells [4].

Biological context of btl

  • Biochemical and genetic analysis indicated that the minimum btl enhancer includes binding sites of Anterior-open [5].
  • These results strongly suggest that the Btl orthologs, BmBtl and SfBtl, are the receptors for vFGF, which mediate vFGF-induced host cell chemotaxis [6].
  • A potential binding site that matches this consensus is found in both Btl and Htl, located between the transmembrane and kinase domains of each receptor [7].
  • Abnormalities in cell migration appear to be a common denominator for the btl defects in these two disparate tissues [8].
  • We examined molecular structures and expression of DFR1 and DFR2, two Drosophila genes closely related to vertebrate FGF-receptor genes [9].

Anatomical context of btl


Associations of btl with chemical compounds

  • Moreover, both Heartless- and Breathless-dependent MAPK activation is significantly reduced in embryos which fail to synthesize heparan sulfate glycosaminoglycans [12].
  • This tyrosine residue appears to be conserved in human FGFR-1 and mediates the association with the adapter protein CrkII, but no association between dCrk (Drosophila homologue of CrkII) and the activated FGFRs was detected [7].

Physical interactions of btl


Regulatory relationships of btl

  • These results indicate that through activation of its target genes, vvl makes the tracheal cells competent to further signalling and suggest that the btl transduction pathway could collaborate with other transduction pathways also regulated by vvl to specify the tracheal branching pattern [14].
  • Overexpression of wild type pgant35A under control of the trachea-specific breathless (btl) promoter results in partial rescue of the lethality [15].

Other interactions of btl


Analytical, diagnostic and therapeutic context of btl

  • Sequence analysis showed that BmBtl is composed of 856 amino acid residues, which potentially encodes a 97.3-kDa polypeptide and shares structural features and sequence similarities with the FGF receptor family [6].
  • Rescue of tracheal migration in btl mutant embryos by the chimeric construct provides a sensitive biological assay for the activity of other Drosophila receptor tyrosine kinases (RTKs) [19].


  1. sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Hacohen, N., Kramer, S., Sutherland, D., Hiromi, Y., Krasnow, M.A. Cell (1998) [Pubmed]
  2. Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Dammai, V., Adryan, B., Lavenburg, K.R., Hsu, T. Genes Dev. (2003) [Pubmed]
  3. Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect mesoderm induction and patterning. Nutt, S.L., Dingwell, K.S., Holt, C.E., Amaya, E. Genes Dev. (2001) [Pubmed]
  4. Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system. Lee, T., Hacohen, N., Krasnow, M., Montell, D.J. Genes Dev. (1996) [Pubmed]
  5. Ligand-dependent activation of breathless FGF receptor gene in Drosophila developing trachea. Ohshiro, T., Emori, Y., Saigo, K. Mech. Dev. (2002) [Pubmed]
  6. Lepidopteran ortholog of Drosophila breathless is a receptor for the baculovirus fibroblast growth factor. Katsuma, S., Daimon, T., Mita, K., Shimada, T. J. Virol. (2006) [Pubmed]
  7. p120 Ras GTPase-activating protein associates with fibroblast growth factor receptors in Drosophila. Woodcock, S.A., Hughes, D.A. Biochem. J. (2004) [Pubmed]
  8. breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. Klämbt, C., Glazer, L., Shilo, B.Z. Genes Dev. (1992) [Pubmed]
  9. Two FGF-receptor homologues of Drosophila: one is expressed in mesodermal primordium in early embryos. Shishido, E., Higashijima, S., Emori, Y., Saigo, K. Development (1993) [Pubmed]
  10. Fibroblast growth factor receptor-dependent morphogenesis of the Drosophila mesoderm. Wilson, R., Leptin, M. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2000) [Pubmed]
  11. branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Sutherland, D., Samakovlis, C., Krasnow, M.A. Cell (1996) [Pubmed]
  12. Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development. Lin, X., Buff, E.M., Perrimon, N., Michelson, A.M. Development (1999) [Pubmed]
  13. Transcriptional regulation of breathless FGF receptor gene by binding of TRACHEALESS/dARNT heterodimers to three central midline elements in Drosophila developing trachea. Ohshiro, T., Saigo, K. Development (1997) [Pubmed]
  14. ventral veinless, a POU domain transcription factor, regulates different transduction pathways required for tracheal branching in Drosophila. Llimargas, M., Casanova, J. Development (1997) [Pubmed]
  15. A UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferase Is Required for Epithelial Tube Formation. Tian, E., Hagen, K.G. J. Biol. Chem. (2007) [Pubmed]
  16. Identification of FGF-dependent genes in the Drosophila tracheal system. Stahl, M., Schuh, R., Adryan, B. Gene Expr. Patterns (2007) [Pubmed]
  17. The breathless FGF receptor homolog, a downstream target of Drosophila C/EBP in the developmental control of cell migration. Murphy, A.M., Lee, T., Andrews, C.M., Shilo, B.Z., Montell, D.J. Development (1995) [Pubmed]
  18. Analysis of the transcriptional activation domain of the Drosophila tango bHLH-PAS transcription factor. Sonnenfeld, M.J., Delvecchio, C., Sun, X. Dev. Genes Evol. (2005) [Pubmed]
  19. Elucidation of the role of breathless, a Drosophila FGF receptor homolog, in tracheal cell migration. Reichman-Fried, M., Dickson, B., Hafen, E., Shilo, B.Z. Genes Dev. (1994) [Pubmed]
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