Gene Symbol: btl
Description: breathless
Alias: 0844/01, BTL/FGFR2, Btl, CG32134, CG6714, CT20816, D-FGFR, DFGF-R1, DFR2, Dfr-2, DmHD-311, Dmel\CG32134, Dtk2, FGFR, FGFR1, Fgf-r, HD-311, Tk2, dFGFR, dev, dtk2, fgf-r, l(3)00208, lambdatop, breathless, CG32134-PA, CG32134-PB, FGF receptor, FGFR, Fibroblast-growth-factor-receptor, btl-PA, btl-PB, devenir, fibrobast growth factor receptor, fibroblast growth factor receptor, fibroblast growth factor receptor 1, no terminal cell clones-L
Species: fruit fly
Products:     btl

Top Publications

  1. Sato M, Kitada Y, Tabata T. Larval cells become imaginal cells under the control of homothorax prior to metamorphosis in the Drosophila tracheal system. Dev Biol. 2008;318:247-57 pubmed publisher
    ..During metamorphosis of less derived species of holometabolous insects, adult structures are known to be formed via cells constituting larval structures. Thus, the Drosophila tracheal system may utilize ancestral mode of metamorphosis. ..
  2. Ikeya T, Hayashi S. Interplay of Notch and FGF signaling restricts cell fate and MAPK activation in the Drosophila trachea. Development. 1999;126:4455-63 pubmed
    ..tracheal system is triggered by the FGF-like ligand Branchless that activates a receptor tyrosine kinase Breathless and the MAP kinase pathway...
  3. Vincent S, Wilson R, Coelho C, Affolter M, Leptin M. The Drosophila protein Dof is specifically required for FGF signaling. Mol Cell. 1998;2:515-25 pubmed
    ..We have identified a component of the FGF receptor (FGFR) signal transduction pathway, Downstream of FGFR (Dof)...
  4. Hemphälä J, Uv A, Cantera R, Bray S, Samakovlis C. Grainy head controls apical membrane growth and tube elongation in response to Branchless/FGF signalling. Development. 2003;130:249-58 pubmed
  5. Chen C, Kühnlein R, Eulenberg K, Vincent S, Affolter M, Schuh R. The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development. Development. 1998;125:4959-68 pubmed
    ..Furthermore, we provide evidence that the border between cells acquiring dorsal branch and dorsal trunk identity is established by the direct interaction of KNIRPS with a spalt cis-regulatory element. ..
  6. Jarecki J, Johnson E, Krasnow M. Oxygen regulation of airway branching in Drosophila is mediated by branchless FGF. Cell. 1999;99:211-20 pubmed
    ..Thus, a single growth factor is reiteratively used to pattern each level of airway branching, and the change in branch patterning results from a switch from developmental to physiological control of its expression. ..
  7. Brodu V, Casanova J. The RhoGAP crossveinless-c links trachealess and EGFR signaling to cell shape remodeling in Drosophila tracheal invagination. Genes Dev. 2006;20:1817-28 pubmed
    ..Our results identify a developmental pathway linking cell fate genes and cell signaling pathways to intracellular modifications during tracheal cell invagination. ..
  8. Gervais L, Casanova J. The Drosophila homologue of SRF acts as a boosting mechanism to sustain FGF-induced terminal branching in the tracheal system. Development. 2011;138:1269-74 pubmed publisher
    ..Our results indicate that DSRF acts as an amplifying step to sustain the progression of terminal branch elongation even in the wild-type conditions of FGF signalling. ..
  9. Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow M. sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell. 1998;92:253-63 pubmed
    ..In wild-type embryos, the Branchless FGF induces secondary branching by activating the Breathless FGF receptor near the tips of growing primary branches...

More Information


  1. Ghabrial A, Krasnow M. Social interactions among epithelial cells during tracheal branching morphogenesis. Nature. 2006;441:746-9 pubmed
    ..These roles are not pre-specified; rather, there is competition between cells such that those with the highest FGF receptor activity take the lead positions, whereas those with less FGF receptor activity assume subsidiary positions and ..
  2. Jarvis L, Toering S, Simon M, Krasnow M, Smith Bolton R. Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development. 2006;133:1133-42 pubmed
    ..We propose that this double-negative feedback circuit shapes the output profile of RTK signaling events. ..
  3. Glazer L, Shilo B. The Drosophila FGF-R homolog is expressed in the embryonic tracheal system and appears to be required for directed tracheal cell extension. Genes Dev. 1991;5:697-705 pubmed
    The Drosophila homolog of the vertebrate fibroblast growth factor receptor (FGF-R) was isolated by low-stringency hybridization...
  4. Metzger R, Krasnow M. Genetic control of branching morphogenesis. Science. 1999;284:1635-9 pubmed
    ..The reiterative use of a signaling pathway by both insects and mammals suggests a general scheme for patterning branching morphogenesis. ..
  5. Jeon M, Zinn K. Receptor tyrosine phosphatases control tracheal tube geometries through negative regulation of Egfr signaling. Development. 2009;136:3121-9 pubmed publisher
    ..PTPRJ corresponds to the murine Scc1 (suppressor of colon cancer) gene. ..
  6. Ohshiro T, Saigo K. Transcriptional regulation of breathless FGF receptor gene by binding of TRACHEALESS/dARNT heterodimers to three central midline elements in Drosophila developing trachea. Development. 1997;124:3975-86 pubmed
    ..of Drosophila trachea is under the control of spatially and/or quantitatively regulated activity of BREATHLESS FGF receptor, which is also essential for midline glial migration...
  7. Emori Y, Saigo K. Distinct expression of two Drosophila homologs of fibroblast growth factor receptors in imaginal discs. FEBS Lett. 1993;332:111-4 pubmed
    ..DFR1 mRNA was observed in several imaginal discs, whereas DFR2 mRNA was not detected...
  8. Samakovlis C, Hacohen N, Manning G, Sutherland D, Guillemin K, Krasnow M. Development of the Drosophila tracheal system occurs by a series of morphologically distinct but genetically coupled branching events. Development. 1996;122:1395-407 pubmed
    ..We further show that the breathless FGF receptor, a tracheal gene required for primary branching, is also required to activate expression of markers involved in ..
  9. Lin X, Buff E, Perrimon N, Michelson A. Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development. Development. 1999;126:3715-23 pubmed
    ..Consistent with an involvement of Sulfateless and Sugarless in fibroblast growth factor receptor signaling, a constitutively activated form of Heartless partially rescues sugarless and sulfateless ..
  10. Klämbt C, Glazer L, Shilo B. breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. Genes Dev. 1992;6:1668-78 pubmed
    ..Hypomorphic alleles exhibit partial migration of all tracheal branches; thus, the locus was termed breathless (btl)...
  11. Dammai V, Adryan B, Lavenburg K, Hsu T. Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Genes Dev. 2003;17:2812-24 pubmed
    ..This phenotype can be suppressed by reducing the dosage of the chemotactic FGF receptor (FGFR) homolog, breathless (btl), indicating that btl and awd are functionally antagonists...
  12. Hu N, Castelli Gair J. Study of the posterior spiracles of Drosophila as a model to understand the genetic and cellular mechanisms controlling morphogenesis. Dev Biol. 1999;214:197-210 pubmed
    ..This results in a spiracle without a lumen and with the tracheal opening located outside it. ..
  13. Guha A, Lin L, Kornberg T. Regulation of Drosophila matrix metalloprotease Mmp2 is essential for wing imaginal disc:trachea association and air sac tubulogenesis. Dev Biol. 2009;335:317-26 pubmed publisher
    ..These findings demonstrate a critical role for Mmp2 in tubulogenesis post-induction, and implicate Mmp2 in regulating dynamic and essential changes to the extracellular matrix. ..
  14. Weaver M, Krasnow M. Dual origin of tissue-specific progenitor cells in Drosophila tracheal remodeling. Science. 2008;321:1496-9 pubmed publisher
    ..Thus, Drosophila pupal/adult tissue progenitors can arise both by early allocation of multipotent cells and late return of differentiated cells to a multipotent state, even within a single tissue. ..
  15. Itoh N, Ornitz D. Evolution of the Fgf and Fgfr gene families. Trends Genet. 2004;20:563-9 pubmed
    ..By contrast, the Fgfr family has expanded only in the second phase...
  16. Forni J, Romani S, Doherty P, Tear G. Neuroglian and FasciclinII can promote neurite outgrowth via the FGF receptor Heartless. Mol Cell Neurosci. 2004;26:282-91 pubmed
    ..We also show that the signal provided by the CAMs acts via the Heartless fibroblast growth factor receptor (FGFR) as outgrowth is reduced to basal levels in the presence of an FGFR inhibitor or if Heartless ..
  17. Cela C, Llimargas M. Egfr is essential for maintaining epithelial integrity during tracheal remodelling in Drosophila. Development. 2006;133:3115-25 pubmed
    ..We find that regulation of MAPK pathway activity by Breathless signalling does not impinge on tissue integrity...
  18. Reichman Fried M, Dickson B, Hafen E, Shilo B. Elucidation of the role of breathless, a Drosophila FGF receptor homolog, in tracheal cell migration. Genes Dev. 1994;8:428-39 pubmed
    DFGF-R1 (breathless), a Drosophila FGF receptor homolog, is required for the migration of tracheal cells and the posterior midline glial cells during embryonic development...
  19. Fradkin L, van Schie M, Wouda R, de Jong A, Kamphorst J, Radjkoemar Bansraj M, et al. The Drosophila Wnt5 protein mediates selective axon fasciculation in the embryonic central nervous system. Dev Biol. 2004;272:362-75 pubmed
    ..Finally, we demonstrate that transcriptional repression of wnt5 in AC neurons by the recently described Wnt5 receptor, Derailed, contributes to this largely posterior commissural localization of Wnt5 protein...
  20. Affolter M, Shilo B. Genetic control of branching morphogenesis during Drosophila tracheal development. Curr Opin Cell Biol. 2000;12:731-5 pubmed
    ..More than 30 genes have been identified and ordered into sequential steps controlling branching morphogenesis. These studies have revealed a number of important principles that might be conserved in other systems. ..
  21. Ohshiro T, Emori Y, Saigo K. Ligand-dependent activation of breathless FGF receptor gene in Drosophila developing trachea. Mech Dev. 2002;114:3-11 pubmed
    Spatially and temporally regulated activity of Branchless/Breathless signaling is essential for trachea development in Drosophila...
  22. Kato K, Chihara T, Hayashi S. Hedgehog and Decapentaplegic instruct polarized growth of cell extensions in the Drosophila trachea. Development. 2004;131:5253-61 pubmed
    ..Orthogonal expression of Hedgehog and Decapentaplegic in the epidermis instructs monopolar extension of the terminal branch along the posterior compartment, thereby matching the pattern of airway growth with that of the epidermis. ..
  23. Myat M, Lightfoot H, Wang P, Andrew D. A molecular link between FGF and Dpp signaling in branch-specific migration of the Drosophila trachea. Dev Biol. 2005;281:38-52 pubmed
    ..The new mutations included novel hypomorphic alleles of the FGF receptor gene, breathless, and the ETS-domain transcription factor gene, pointed...
  24. Reichman Fried M, Shilo B. Breathless, a Drosophila FGF receptor homolog, is required for the onset of tracheal cell migration and tracheole formation. Mech Dev. 1995;52:265-73 pubmed
    Breathless, a Drosophila FGF receptor homolog (DFGF-R1), was shown to be essential for the migration of the tracheal cells and the posterior midline glia cells...
  25. Mortimer N, Moberg K. Regulation of Drosophila embryonic tracheogenesis by dVHL and hypoxia. Dev Biol. 2009;329:294-305 pubmed publisher
    ..a program of branching and growth driven by HIF-1alpha/sima-dependent expression of the breathless (btl) FGF receptor. By contrast, the ability of the developing embryonic tracheal system to respond to hypoxia and integrate hard-..
  26. Wang Q, Uhlirova M, Bohmann D. Spatial restriction of FGF signaling by a matrix metalloprotease controls branching morphogenesis. Dev Cell. 2010;18:157-64 pubmed publisher
    ..The signaling function for MMPs described here may not be limited to branching morphogenesis processes. ..
  27. Schottenfeld Roames J, Ghabrial A. Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth. Nat Cell Biol. 2012;14:386-93 pubmed publisher
    ..Thus, vesicle trafficking has key roles in making and shaping seamless tubes...
  28. Srahna M, Leyssen M, Choi C, Fradkin L, Noordermeer J, Hassan B. A signaling network for patterning of neuronal connectivity in the Drosophila brain. PLoS Biol. 2006;4:e348 pubmed
    ..The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF)-Breathless (FGF receptor) axon-retracting signal to modulate JNK activity...
  29. Llimargas M, Lawrence P. Seven Wnt homologues in Drosophila: a case study of the developing tracheae. Proc Natl Acad Sci U S A. 2001;98:14487-92 pubmed
    ..We suggest that the main advantage of retaining a number of similar genes is that it allows more subtle forms of control and more flexibility during evolution. ..
  30. Dossenbach C, Rock S, Affolter M. Specificity of FGF signaling in cell migration in Drosophila. Development. 2001;128:4563-72 pubmed model systems, we find that the intracellular domain of the fibroblast growth factor receptors (FGFRs) Breathless (Btl) and Heartless (Htl) can be functionally replaced by the intracellular domains of Torso (Tor) and epidermal ..
  31. Bradley P, Andrew D. ribbon encodes a novel BTB/POZ protein required for directed cell migration in Drosophila melanogaster. Development. 2001;128:3001-15 pubmed
    ..Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development. ..
  32. Sato M, Kornberg T. FGF is an essential mitogen and chemoattractant for the air sacs of the drosophila tracheal system. Dev Cell. 2002;3:195-207 pubmed
  33. Wilk R, Weizman I, Shilo B. trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila. Genes Dev. 1996;10:93-102 pubmed
    ..The role of Trachealess in the formation of several tubular tissues in the embryo suggests that it may induce a general fate of branched tubular structures of epithelial origin. ..
  34. Ghabrial A, Levi B, Krasnow M. A systematic screen for tube morphogenesis and branching genes in the Drosophila tracheal system. PLoS Genet. 2011;7:e1002087 pubmed publisher
  35. Sutherland D, Samakovlis C, Krasnow M. branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Cell. 1996;87:1091-101 pubmed
    ..growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase, an FGF receptor homolog expressed on developing tracheal cells...
  36. Jones T, Metzstein M. A novel function for the PAR complex in subcellular morphogenesis of tracheal terminal cells in Drosophila melanogaster. Genetics. 2011;189:153-64 pubmed publisher
    ..Our results demonstrate that proteins from the PAR complex can be deployed independently within a single cell to control two different morphogenetic processes. ..
  37. Roy S, Hsiung F, Kornberg T. Specificity of Drosophila cytonemes for distinct signaling pathways. Science. 2011;332:354-8 pubmed publisher
  38. Rosin D, Shilo B. Branch-specific migration cues in the Drosophila tracheal system. Bioessays. 2002;24:110-3 pubmed
    ..Bnl triggers the activation of the FGF receptor Breathless (Btl) locally in all tracheal cells...
  39. Yan D, Lin X. Drosophila glypican Dally-like acts in FGF-receiving cells to modulate FGF signaling during tracheal morphogenesis. Dev Biol. 2007;312:203-16 pubmed
    Previous studies in Drosophila have shown that heparan sulfate proteoglycans (HSPGs) are involved in both breathless (btl)- and heartless (htl)-mediated FGF signaling during embryogenesis...
  40. Centanin L, Dekanty A, Romero N, Irisarri M, Gorr T, Wappner P. Cell autonomy of HIF effects in Drosophila: tracheal cells sense hypoxia and induce terminal branch sprouting. Dev Cell. 2008;14:547-58 pubmed publisher
    ..This response involves the upregulation of FGF/Branchless in hypoxic tissues, which binds its receptor Breathless on tracheal cells...
  41. Ribeiro C, Ebner A, Affolter M. In vivo imaging reveals different cellular functions for FGF and Dpp signaling in tracheal branching morphogenesis. Dev Cell. 2002;2:677-83 pubmed
    ..Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such, and Dpp controls cellular functions allowing branch morphogenesis and outgrowth. ..
  42. Glazer L, Shilo B. Hedgehog signaling patterns the tracheal branches. Development. 2001;128:1599-606 pubmed
    ..Signaling by several pathways, including the Hh pathway, thus serves to subdivide the uniform population of tracheal cells into distinct cell types that will subsequently be recruited into the different branches. ..
  43. Lee T, Hacohen N, Krasnow M, Montell D. Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system. Genes Dev. 1996;10:2912-21 pubmed
    ..We have investigated whether the Drosophila FGF receptor homolog, Breathless (BTL), whose activity is necessary for each phase of branching morphogenesis in the ..
  44. Buff E, Carmena A, Gisselbrecht S, Jimenez F, Michelson A. Signalling by the Drosophila epidermal growth factor receptor is required for the specification and diversification of embryonic muscle progenitors. Development. 1998;125:2075-86 pubmed
    ..Thus, the epidermal growth factor receptor contributes both to muscle progenitor specification and to the diversification of muscle identities. ..
  45. Li Z, Zhang Y, Han L, Shi L, Lin X. Trachea-derived dpp controls adult midgut homeostasis in Drosophila. Dev Cell. 2013;24:133-43 pubmed publisher
    ..This work will provide important insights into the mechanisms of tissue homeostasis control by interorgan communication...
  46. Ruiz O, Nikolova L, Metzstein M. Drosophila Zpr1 (Zinc finger protein 1) is required downstream of both EGFR and FGFR signaling in tracheal subcellular lumen formation. PLoS ONE. 2012;7:e45649 pubmed publisher
    ..We provide evidence that this alternative pathway may involve fibroblast growth factor receptor (FGFR) signaling...
  47. Montell D. The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. Development. 1999;126:3035-46 pubmed
    ..New types of genetic screens promise to fill in some of these gaps in the near future. ..
  48. Llimargas M, Casanova J. EGF signalling regulates cell invagination as well as cell migration during formation of tracheal system in Drosophila. Dev Genes Evol. 1999;209:174-9 pubmed
    ..The combined action of the Decapentaplegic (Dpp), Epidermal growth factor (EGF) and breathless/branchless pathways are thought to be responsible for the pattern of tracheal branches...
  49. Llimargas M, Casanova J. ventral veinless, a POU domain transcription factor, regulates different transduction pathways required for tracheal branching in Drosophila. Development. 1997;124:3273-81 pubmed
    ..Morphogenesis of the tracheal tree requires the activity of many genes, among them breathless (btl) and ventral veinless (vvl) whose mutations abolish tracheal cell migration...
  50. Nelson W. Tube morphogenesis: closure, but many openings remain. Trends Cell Biol. 2003;13:615-21 pubmed
    ..This review provides a summary of these pathways based upon articles published in the Tube Morphogenesis Series in Trends in Cell Biology. ..
  51. Shishido E, Higashijima S, Emori Y, Saigo K. Two FGF-receptor homologues of Drosophila: one is expressed in mesodermal primordium in early embryos. Development. 1993;117:751-61 pubmed
    ..We examined molecular structures and expression of DFR1 and DFR2, two Drosophila genes closely related to vertebrate FGF-receptor genes...
  52. Queenan A, Ghabrial A, Schupbach T. Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Development. 1997;124:3871-80 pubmed
    ..This result indicates that subpopulations of follicle cells along the anterior/posterior axis can respond to Top/Egfr activation independently of one another. ..
  53. Baer M, Bilstein A, Caussinus E, Csiszar A, Affolter M, Leptin M. The role of apoptosis in shaping the tracheal system in the Drosophila embryo. Mech Dev. 2010;127:28-35 pubmed publisher
    ..Extruded cells die and are engulfed by macrophages. Our results suggest that the pattern of cell extrusion and death is not hard-wired, but is determined by environmental cues. ..
  54. Jones N, Kuo Y, Sun Y, Beckendorf S. The Drosophila Pax gene eye gone is required for embryonic salivary duct development. Development. 1998;125:4163-74 pubmed
    ..In addition to its role in the salivary duct, eye gone is required in the embryo for the development of the eye-antennal imaginal disc and the chemosensory antennal organ. ..
  55. Petit V, Nussbaumer U, Dossenbach C, Affolter M. Downstream-of-FGFR is a fibroblast growth factor-specific scaffolding protein and recruits Corkscrew upon receptor activation. Mol Cell Biol. 2004;24:3769-81 pubmed
    Fibroblast growth factor (FGF) receptor (FGFR) signaling controls the migration of glial, mesodermal, and tracheal cells in Drosophila melanogaster...
  56. Gabay L, Seger R, Shilo B. MAP kinase in situ activation atlas during Drosophila embryogenesis. Development. 1997;124:3535-41 pubmed
    ..Since the antibody was raised against the phosphorylated form of a conserved ERK peptide containing the TEY motif, this approach is applicable to a wide spectrum of multicellular organisms. ..
  57. Michelson A, Gisselbrecht S, Buff E, Skeath J. Heartbroken is a specific downstream mediator of FGF receptor signalling in Drosophila. Development. 1998;125:4379-89 pubmed
    ..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.
  58. Imam F, Sutherland D, Huang W, Krasnow M. stumps, a Drosophila gene required for fibroblast growth factor (FGF)-directed migrations of tracheal and mesodermal cells. Genetics. 1999;152:307-18 pubmed
    ..The results suggest that stumps function promotes FGF-directed cell migrations, either by potentiating the FGF signaling process or by coupling the signal to the cellular machinery required for directed cell movement. ..
  59. Caviglia S, Luschnig S. The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity. Development. 2013;140:1240-9 pubmed publisher
    ..The switch from a branching towards an anastomosing tip cell type may have evolved with the acquisition of a main tube that connects separate tracheal primordia to generate a tubular network. ..
  60. Okenve Ramos P, Llimargas M. Fascin links Btl/FGFR signalling to the actin cytoskeleton during Drosophila tracheal morphogenesis. Development. 2014;141:929-39 pubmed publisher
    ..Tracheal cell migration requires the Breathless/FGFR pathway; however, how the pathway induces migration remains poorly understood...
  61. Tanaka Matakatsu M, Uemura T, Oda H, Takeichi M, Hayashi S. Cadherin-mediated cell adhesion and cell motility in Drosophila trachea regulated by the transcription factor Escargot. Development. 1996;122:3697-705 pubmed
  62. Chanut Delalande H, Jung A, Lin L, Baer M, Bilstein A, Cabernard C, et al. A genetic mosaic analysis with a repressible cell marker screen to identify genes involved in tracheal cell migration during Drosophila air sac morphogenesis. Genetics. 2007;176:2177-87 pubmed
    Branching morphogenesis of the Drosophila tracheal system relies on the fibroblast growth factor receptor (FGFR) signaling pathway...