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

• Spatially and temporally regulated activity of Branchless/Breathless signaling is essential for trachea development in Drosophila [5].
• breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells [8].
• DFR2 expression occurs in endodermal precursor cells, CNS midline cells and certain ectodermal cells such as those of trachea and salivary duct [9].
• The Drosophila fibroblast growth factor (FGF) receptors Heartless and Breathless are required for the morphogenesis of the mesoderm and the tracheal system [10].
• Generalized misexpression activates later programs of tracheal gene expression and branching, resulting in massive networks of branches. bnl encodes a homolog of mammalian fibroblast 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 [11].

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

• Transcriptional regulation of breathless FGF receptor gene by binding of TRACHEALESS/dARNT heterodimers to three central midline elements in Drosophila developing trachea [13].

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

• The downstream targets of the Bnl/Btl signalling cascade, however, remain mostly unknown [16].
• Branchless/Breathless signaling includes a Sprouty-dependent negative feedback loop [5].
• Furthermore, C/EBP-independent btl expression was able to rescue the migration defects of hypomorphic slbo alleles [17].
• Transcriptional activation of the fibroblast growth factor receptor (breathless) gene required an intact TGO C-terminus, in vitro [18].
• 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 [14].

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].

References