btl

UniProt ID: Q09147
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Breathless (Btl) is one of the two Drosophila fibroblast growth factor receptors (FGFR2 homolog), a single-pass type I transmembrane receptor tyrosine kinase with five extracellular Ig-like domains and a cytoplasmic split tyrosine kinase domain. Its ligand is the FGF Branchless (Bnl). Bnl binding at the plasma membrane and on cytonemes activates Btl, which phosphorylates and signals through the FGFR-specific adaptor Dof/Stumps/Heartbroken, recruiting Corkscrew (SHP2), Src64B and Ras to activate the MAPK cascade. Btl is expressed in the developing tracheal system, midline glia and several other cell types. Its best-defined role is in tracheal (respiratory) system morphogenesis: Btl activity directs chemotactic migration of tracheal epithelial cells toward Bnl sources to form primary branches, selects tip cells, and, in a dose-dependent way, specifies secondary and terminal branch cell fates. It also drives filopodial activity, larval terminal branching and adult air sac formation. In other contexts Btl contributes to midline and retinal glial migration, border cell migration in the ovary, eye disc morphogenesis, axon retraction in the adult brain, and maintenance of lymph gland blood progenitors.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001667 ameboidal-type cell migration
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted ameboidal-type cell migration; true but entailed by the experimental border follicle cell migration and tracheal epithelial cell migration rows.
Reason: Btl drives FGF-guided migration of tracheal cells and border cells; GO:0007427 and GO:0007298, both is_a descendants of this term, are accepted/kept elsewhere in this review, so the generic ARBA term adds nothing.
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0001708 cell fate specification
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted cell fate specification; true, entailed by terminal cell fate specification and epithelial cell type specification (open tracheal system).
Reason: Btl activity levels specify terminal and tip-cell fates (GO:0035154, GO:0035153 retained in this review), which entail this generic term.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0001745 compound eye morphogenesis
IMP
PMID:22384378
Genetic analysis of fibroblast growth factor signaling in th...
KEEP AS NON CORE
Summary: Bnl/Btl signalling regulates epithelial reorganization during eye disc and pupal eye development.
Reason: Experimental (IMP, full text read). A real but peripheral context of the same FGF receptor activity; not the defining role of btl.
Supporting Evidence:
PMID:22384378
Breathless (Btl) functions as the fibroblast growth factor receptor to mediate Bnl signal, and together they regulate expression of DE-cadherin, Crumbs, and Actin.
GO:0003006 developmental process involved in reproduction
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted developmental process involved in reproduction; entailed by border follicle cell migration.
Reason: The only reproductive context with btl evidence is ovarian border cell migration (GO:0007298, a descendant via oogenesis), kept elsewhere; the generic term is uninformative.
Supporting Evidence:
PMID:7671793
btl mutations dominantly enhanced the border cell migration defects found in weak slbo alleles
GO:0004672 protein kinase activity
IEA
GO_REF:0000002
MODIFY
Summary: InterPro-based kinase activity prediction; correct but less specific than the FGF receptor activity supported for Btl.
Reason: Btl is a receptor tyrosine kinase of the FGFR subfamily with a conserved split kinase domain, and its ligand (Bnl) and FGFR-specific substrate/adaptor (Dof) are known. Replace with GO:0005007, which the gene already carries by IDA/IGI/IMP.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
PMID:15082772
expression of constitutive active Btl or Htl led to strong tyrosine phosphorylation of Dof, demonstrating that Dof is indeed a phosphotarget, either a direct or an indirect one, of both Drosophila FGFRs
GO:0004713 protein tyrosine kinase activity
IEA
GO_REF:0000120
MODIFY
Summary: InterPro-based kinase activity prediction; correct but less specific than the FGF receptor activity supported for Btl.
Reason: Btl is a receptor tyrosine kinase of the FGFR subfamily with a conserved split kinase domain, and its ligand (Bnl) and FGFR-specific substrate/adaptor (Dof) are known. Replace with GO:0005007, which the gene already carries by IDA/IGI/IMP.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
PMID:15082772
expression of constitutive active Btl or Htl led to strong tyrosine phosphorylation of Dof, demonstrating that Dof is indeed a phosphotarget, either a direct or an indirect one, of both Drosophila FGFRs
GO:0004714 transmembrane receptor protein tyrosine kinase activity
IBA
GO_REF:0000033
MODIFY
Summary: PAINT IBA for transmembrane receptor protein tyrosine kinase activity; correct, and Btl lies within the RTK clade, but the more specific FGFR activity is supported.
Reason: The IBA is sound (Btl is an FGFR-subfamily RTK, and appears among its own sources because of its experimental FGFR annotations), but GO:0005007 fibroblast growth factor receptor activity, an is_a descendant already carried by the gene with experimental support, is the precise function.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Sources checked:
PANTHER:PTN001230349 Β· PTN001230349 SUPPORTS TRANSFER
RTK node; Btl lies inside the clade and is itself an experimentally characterized FGFR. The propagated term is correct but less specific than GO:0005007.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
PMID:8978613
bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase
GO:0004714 transmembrane receptor protein tyrosine kinase activity
IEA
GO_REF:0000003
MODIFY
Summary: EC 2.7.10.1 mapping to transmembrane RTK activity; correct but general.
Reason: Same claim as the IBA row; the precise supported activity is GO:0005007 FGFR activity.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
GO:0005007 fibroblast growth factor receptor activity
IDA
PMID:15082772
Downstream-of-FGFR is a fibroblast growth factor-specific sc...
ACCEPT
Summary: Activated Btl drives tyrosine phosphorylation of, and forms a complex with, the FGFR-specific adaptor Dof in S2 cells.
Reason: Core molecular function: Btl is the FGF receptor tyrosine kinase that binds Branchless and signals through Dof/Csw to Ras-MAPK. Rows for this term reinforce each other.
Supporting Evidence:
PMID:15082772
expression of constitutive active Btl or Htl led to strong tyrosine phosphorylation of Dof, demonstrating that Dof is indeed a phosphotarget, either a direct or an indirect one, of both Drosophila FGFRs
PMID:15082772
full-length Dof or the minimal Dof600 protein formed a complex with the activated version of both Drosophila FGFRs upon induction
GO:0005007 fibroblast growth factor receptor activity
IDA
PMID:30328809
Feedback regulation of cytoneme-mediated transport shapes a ...
ACCEPT
Summary: Endogenous Bnl:GFP ligand is entirely receptor-bound, colocalizing with endogenous Btl:Cherry in air sac primordium cells and cytonemes.
Reason: Core molecular function: Btl is the FGF receptor tyrosine kinase that binds Branchless and signals through Dof/Csw to Ras-MAPK. Rows for this term reinforce each other.
Supporting Evidence:
PMID:30328809
In trans-heterozygous btl:cherryendo/bnl:gfpendo animals, all the Bnl:GFP puncta in the ASP colocalized with Btl:Cherry and the receptor gradient coincided with that of the ligand gradient
PMID:30328809
Densely packed Btl:Cherry molecules were visualized on the surface of the ASP cytonemes
GO:0005007 fibroblast growth factor receptor activity
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA prediction of FGFR activity; consistent with family membership and experimental data.
Reason: Core molecular function: Btl is the FGF receptor tyrosine kinase that binds Branchless and signals through Dof/Csw to Ras-MAPK. Rows for this term reinforce each other.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
PMID:8978613
bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase
GO:0005007 fibroblast growth factor receptor activity
IGI
PMID:8978613
branchless encodes a Drosophila FGF homolog that controls tr...
ACCEPT
Summary: Genetic interaction with bnl identifies Branchless FGF as the Btl ligand.
Reason: Core molecular function: Btl is the FGF receptor tyrosine kinase that binds Branchless and signals through Dof/Csw to Ras-MAPK. Rows for this term reinforce each other.
Supporting Evidence:
PMID:8978613
bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase
GO:0005007 fibroblast growth factor receptor activity
IMP
PMID:8918892
Regulated Breathless receptor tyrosine kinase activity requi...
ACCEPT
Summary: Constitutively active and reduced Btl alter tracheal migration and branching fates, showing Btl receptor activity is instructive.
Reason: Core molecular function: Btl is the FGF receptor tyrosine kinase that binds Branchless and signals through Dof/Csw to Ras-MAPK. Rows for this term reinforce each other.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0005515 protein binding
IPI
PMID:15082772
Downstream-of-FGFR is a fibroblast growth factor-specific sc...
REMOVE
Summary: IPI with Dof (Stumps/Heartbroken) by co-immunoprecipitation in S2 cells.
Reason: Generic protein binding is uninformative; the interaction itself is real (activated Btl forms a complex with Dof) and is captured functionally by FGFR activity and the FGFR signaling pathway. Removal does not dispute the interaction.
Supporting Evidence:
PMID:15082772
full-length Dof or the minimal Dof600 protein formed a complex with the activated version of both Drosophila FGFRs upon induction
GO:0005524 ATP binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: ATP binding inferred from the protein kinase ATP-binding motif.
Reason: True of the kinase domain (ATP-binding site predicted by PROSITE rule) but a cofactor property subsumed by the kinase/receptor activity rather than a function in itself.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
/ligand="ATP"
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Btl is a single-pass type I transmembrane receptor at the plasma membrane.
Reason: Plasma membrane is where Btl binds Bnl and signals; supported by Btl-GFP localization (IDA) and topology; the IBA and ARBA rows agree.
Supporting Evidence:
PMID:20422006
In wild type cells, Btl-GFP mostly accumulated at the cell membrane
file:DROME/btl/btl-uniprot.txt
Single-pass type I membrane protein.
GO:0005886 plasma membrane
IDA
PMID:20422006
The Hrs/Stam complex acts as a positive and negative regulat...
ACCEPT
Summary: Btl is a single-pass type I transmembrane receptor at the plasma membrane.
Reason: Plasma membrane is where Btl binds Bnl and signals; supported by Btl-GFP localization (IDA) and topology; the IBA and ARBA rows agree.
Supporting Evidence:
PMID:20422006
In wild type cells, Btl-GFP mostly accumulated at the cell membrane
GO:0005886 plasma membrane
IEA
GO_REF:0000117
ACCEPT
Summary: Btl is a single-pass type I transmembrane receptor at the plasma membrane.
Reason: Plasma membrane is where Btl binds Bnl and signals; supported by Btl-GFP localization (IDA) and topology; the IBA and ARBA rows agree.
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Single-pass type I membrane protein.
PMID:20422006
In wild type cells, Btl-GFP mostly accumulated at the cell membrane
GO:0007276 gamete generation
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted gamete generation; entailed (via oogenesis) by border follicle cell migration.
Reason: Entailed by GO:0007298 border follicle cell migration, kept elsewhere, via oogenesis and female gamete generation; the term is true but uninformative given that more specific row. Btl acts in the somatic border cells, not in germ cells.
Supporting Evidence:
PMID:7671793
btl mutations dominantly enhanced the border cell migration defects found in weak slbo alleles
GO:0007298 border follicle cell migration
IMP
PMID:7671793
The breathless FGF receptor homolog, a downstream target of ...
KEEP AS NON CORE
Summary: btl is a C/EBP (slbo) target in border cells and btl mutations enhance slbo border cell migration defects.
Reason: Experimental and credible, but a modest, partially redundant role; the main guidance receptors for border cells are PVR and EGFR. Non-core context of Btl FGFR activity.
Supporting Evidence:
PMID:7671793
btl mutations dominantly enhanced the border cell migration defects found in weak slbo alleles
GO:0007424 open tracheal system development
IEP
PMID:1849109
The Drosophila FGF-R homolog is expressed in the embryonic t...
ACCEPT
Summary: Expression in the developing tracheal system.
Reason: The claim (btl acts in open tracheal system development) is well established by the IMP rows; IEP alone would be weak but the rows reinforce one another.
Supporting Evidence:
PMID:1849109
the gene is predominantly expressed in a restricted set of tissues: the developing tracheal system and the delaminating midline glial and neural cells
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
file:DROME/btl/btl-deep-research-manual.md
Required for tracheal cell migration and primary branch formation
GO:0007424 open tracheal system development
IMP
PMID:26632449
FGF coordinates air sac development by activation of the EGF...
ACCEPT
Summary: Bnl/Btl signalling controls air sac primordium development via PntP1/PntP2 and Vein.
Reason: Btl is the receptor that drives tracheal (including adult air sac) development.
Supporting Evidence:
PMID:26632449
Bnl-FGF/Btl signaling controls cell migration of the ASP by the up-regulation of PntP1, and vn expression through PntP2
GO:0007424 open tracheal system development
IMP
PMID:31237953
Dual role of FGF in proliferation and endoreplication of Dro...
ACCEPT
Summary: Btl signalling controls proliferation versus endoreplication of larval tracheal progenitors.
Reason: Consistent with the central tracheal role.
Supporting Evidence:
PMID:31237953
Tr5 SB of early and late L3 larva overexpressing a constitutive active form of the FGF receptor btl (Tor-btl).
GO:0007426 tracheal outgrowth, open tracheal system
IMP
PMID:12015974
In vivo imaging reveals different cellular functions for FGF...
ACCEPT
Summary: Live imaging shows Bnl/FGF signalling controls filopodial activity during tracheal branch outgrowth.
Reason: Direct requirement of the Bnl/Btl pathway in branch outgrowth.
Supporting Evidence:
PMID:12015974
Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:11714681
Specificity of FGF signaling in cell migration in Drosophila...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:11714681
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 growth factor receptor (EGFR)
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:12194851
FGF is an essential mitogen and chemoattractant for the air ...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:12194851
These findings provide evidence that FGF is a mitogen in Drosophila
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:1325393
breathless, a Drosophila FGF receptor homolog, is essential ...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:16326394
Distinct roles for two receptor tyrosine kinases in epitheli...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:16326394
Fgf signaling directs cell migration at the tip of the structure
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:1849109
The Drosophila FGF-R homolog is expressed in the embryonic t...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:1849109
the gene is predominantly expressed in a restricted set of tissues: the developing tracheal system and the delaminating midline glial and neural cells
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:20516215
Drosophila von Hippel-Lindau tumor suppressor gene function ...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:20516215
The endocytic function regulates the surface level of the chemotactic signaling receptor Breathless
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:26342211
Ligand-binding and constitutive FGF receptors in single Dros...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:26342211
FGF can act as a chemoattractant rather than as a motogen in collective cell migration
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:8125257
Elucidation of the role of breathless, a Drosophila FGF rece...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:8125257
induction of the chimeric receptor corrected the tracheal defects of breathless (btl) mutant embryos, allowing the tracheal cells to migrate along their normal tracts
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:8541215
Breathless, a Drosophila FGF receptor homolog, is required f...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:8541215
Induction of the construct after the tracheal branches are completed, blocked the formation of tracheoles, i.e. extension of cellular processes by the terminal tracheal cells, demonstrating that Breathless plays an essential role in this process as well.
GO:0007427 epithelial cell migration, open tracheal system
IMP
PMID:8918892
Regulated Breathless receptor tyrosine kinase activity requi...
ACCEPT
Summary: Btl is required for directed migration of tracheal epithelial cells toward Bnl sources.
Reason: Core biological process of btl, supported by many independent loss- and gain-of-function studies (named for this phenotype).
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0007428 primary branching, open tracheal system
IMP
PMID:15848387
A molecular link between FGF and Dpp signaling in branch-spe...
ACCEPT
Summary: Hypomorphic btl alleles reveal roles in branch-specific (dorsal branch) migration.
Reason: Primary branching is the canonical btl requirement.
Supporting Evidence:
PMID:15848387
breathless and pointed control dorsal branch migration through transcriptional regulation of the Dpp pathway effectors, Knirps and Knirps-related
GO:0007428 primary branching, open tracheal system
IMP
PMID:16831830
Egfr is essential for maintaining epithelial integrity durin...
ACCEPT
Summary: Primary branching annotation from a study of Egfr in tracheal remodelling.
Reason: Abstract-only; the abstract shows Btl signalling was manipulated in this study. Primary branching requires btl by many other studies, so defer to the curator.
Supporting Evidence:
PMID:16831830
We find that regulation of MAPK pathway activity by Breathless signalling does not impinge on tissue integrity.
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0007428 primary branching, open tracheal system
IMP
PMID:8625828
Development of the Drosophila tracheal system occurs by a se...
ACCEPT
Summary: btl is required for primary branching and for activation of secondary branching markers.
Reason: Core tracheal branching role.
Supporting Evidence:
PMID:8625828
the breathless FGF receptor, a tracheal gene required for primary branching, is also required to activate expression of markers involved in secondary branching
GO:0007428 primary branching, open tracheal system
IMP
PMID:8918892
Regulated Breathless receptor tyrosine kinase activity requi...
ACCEPT
Summary: Regulated Btl activity patterns migration and branching.
Reason: Core tracheal branching role.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0007429 secondary branching, open tracheal system
IMP
PMID:8625828
Development of the Drosophila tracheal system occurs by a se...
ACCEPT
Summary: btl is required to activate secondary branch markers.
Reason: Secondary branch fates depend on Btl activity.
Supporting Evidence:
PMID:8625828
the breathless FGF receptor, a tracheal gene required for primary branching, is also required to activate expression of markers involved in secondary branching
GO:0007429 secondary branching, open tracheal system
IMP
PMID:8918892
Regulated Breathless receptor tyrosine kinase activity requi...
ACCEPT
Summary: Constitutive Btl induces extra secondary branch-forming cells.
Reason: Quantitative Btl activity specifies secondary branching.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0007430 terminal branching, open tracheal system
IMP
PMID:8541215
Breathless, a Drosophila FGF receptor homolog, is required f...
ACCEPT
Summary: Dominant-negative Btl after branching blocks tracheole (terminal branch) formation.
Reason: Btl required for terminal branching.
Supporting Evidence:
PMID:8541215
Induction of the construct after the tracheal branches are completed, blocked the formation of tracheoles, i.e. extension of cellular processes by the terminal tracheal cells, demonstrating that Breathless plays an essential role in this process as well.
GO:0007430 terminal branching, open tracheal system
IMP
PMID:8918892
Regulated Breathless receptor tyrosine kinase activity requi...
ACCEPT
Summary: Constitutive Btl causes extra terminal branch-forming cells.
Reason: Btl activity specifies terminal branching.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0008284 positive regulation of cell population proliferation
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: IBA: FGFR family node promoting cell proliferation.
Reason: Btl/FGF is a mitogen for air sac precursors; true but a context-dependent output, not the defining role.
Supporting Evidence:
PMID:12194851
These findings provide evidence that FGF is a mitogen in Drosophila
GO:0008284 positive regulation of cell population proliferation
IMP
PMID:12194851
FGF is an essential mitogen and chemoattractant for the air ...
KEEP AS NON CORE
Summary: FGF is an essential mitogen for air sac precursor cells.
Reason: Real but secondary output of Btl signalling.
Supporting Evidence:
PMID:12194851
These findings provide evidence that FGF is a mitogen in Drosophila
GO:0008347 glial cell migration
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA prediction of glial cell migration.
Reason: Consistent with experimental data (midline glia, retinal basal glia); peripheral to the tracheal core role.
Supporting Evidence:
PMID:1325393
In the midline of the mutant embryos, the posterior pair of midline glial cells begins to migrate anteriorly, but fails to reach the posterior commissure.
GO:0008347 glial cell migration
IMP
PMID:1325393
breathless, a Drosophila FGF receptor homolog, is essential ...
KEEP AS NON CORE
Summary: btl mutants show failure of posterior midline glia migration.
Reason: Experimental; second tissue in which Btl-driven migration operates; non-core.
Supporting Evidence:
PMID:1325393
In the midline of the mutant embryos, the posterior pair of midline glial cells begins to migrate anteriorly, but fails to reach the posterior commissure.
GO:0008347 glial cell migration
IMP
PMID:22384378
Genetic analysis of fibroblast growth factor signaling in th...
KEEP AS NON CORE
Summary: Btl in retinal basal glia controls onset and extent of their migration into the eye disc.
Reason: Here Btl restricts precocious migration; the generic glial cell migration term covers the regulatory role.
Supporting Evidence:
PMID:22384378
Bnl expressed by the eye tissue activates nonautonomous Btl signaling in the glial cells to regulate the temporal onset and extent of RBG migration
GO:0008543 fibroblast growth factor receptor signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:8978613
bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase
PMID:9809073
Dof is an intracellular protein that is essential for signal transmission by the FGFR and acts downstream of the receptor and upstream of Ras.
GO:0008543 fibroblast growth factor receptor signaling pathway
IDA
PMID:15082772
Downstream-of-FGFR is a fibroblast growth factor-specific sc...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:15082772
expression of constitutive active Btl or Htl led to strong tyrosine phosphorylation of Dof, demonstrating that Dof is indeed a phosphotarget, either a direct or an indirect one, of both Drosophila FGFRs
GO:0008543 fibroblast growth factor receptor signaling pathway
IDA
PMID:30328809
Feedback regulation of cytoneme-mediated transport shapes a ...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:30328809
In trans-heterozygous btl:cherryendo/bnl:gfpendo animals, all the Bnl:GFP puncta in the ASP colocalized with Btl:Cherry and the receptor gradient coincided with that of the ligand gradient
GO:0008543 fibroblast growth factor receptor signaling pathway
IEP
PMID:12175485
Ligand-dependent activation of breathless FGF receptor gene ...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:12175485
Branchless/Breathless signaling activates MAP-kinase, which in turn, activates late btl expression
GO:0008543 fibroblast growth factor receptor signaling pathway
IGI
PMID:8125257
Elucidation of the role of breathless, a Drosophila FGF rece...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:8125257
induction of the chimeric receptor corrected the tracheal defects of breathless (btl) mutant embryos, allowing the tracheal cells to migrate along their normal tracts
GO:0008543 fibroblast growth factor receptor signaling pathway
IGI
PMID:8125257
Elucidation of the role of breathless, a Drosophila FGF rece...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:8125257
induction of the chimeric receptor corrected the tracheal defects of breathless (btl) mutant embryos, allowing the tracheal cells to migrate along their normal tracts
GO:0008543 fibroblast growth factor receptor signaling pathway
IGI
PMID:8978613
branchless encodes a Drosophila FGF homolog that controls tr...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:8978613
bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase
GO:0008543 fibroblast growth factor receptor signaling pathway
IGI
PMID:9809073
The Drosophila protein Dof is specifically required for FGF ...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:9809073
Dof is an intracellular protein that is essential for signal transmission by the FGFR and acts downstream of the receptor and upstream of Ras.
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:12194851
FGF is an essential mitogen and chemoattractant for the air ...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:12194851
These findings provide evidence that FGF is a mitogen in Drosophila
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:16326394
Distinct roles for two receptor tyrosine kinases in epitheli...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:16326394
Fgf signaling directs cell migration at the tip of the structure
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:20154139
A novel conserved phosphotyrosine motif in the Drosophila fi...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:20154139
Src kinases contribute to FGFR-dependent MAPK activation
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:31237953
Dual role of FGF in proliferation and endoreplication of Dro...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:31237953
Tr5 SB of early and late L3 larva overexpressing a constitutive active form of the FGF receptor btl (Tor-btl).
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:33395389
The vascular niche controls Drosophila hematopoiesis via fib...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:33395389
We established that Bnl is expressed in cardiac cells and signals to its receptor Breathless (Btl) expressed in progenitors.
GO:0008543 fibroblast growth factor receptor signaling pathway
IMP
PMID:9778498
Heartbroken is a specific downstream mediator of FGF recepto...
ACCEPT
Summary: Btl is the receptor of the Bnl FGF signalling pathway.
Reason: Core process: Btl initiates FGFR signalling via Dof, Csw/SHP2, Src64B and Ras-MAPK; rows reinforce each other.
Supporting Evidence:
PMID:9778498
heartbroken is involved in both the HEARTLESS- and BREATHLESS-dependent activation of MAPK
GO:0016020 membrane
IEA
GO_REF:0000044
MODIFY
Summary: UniProt subcellular location keyword mapping to membrane.
Reason: Correct but general; Btl is a single-pass plasma membrane receptor, so replace with GO:0005886 plasma membrane (already carried by IDA).
Proposed replacements: plasma membrane
Supporting Evidence:
file:DROME/btl/btl-uniprot.txt
Single-pass type I membrane protein.
PMID:20422006
In wild type cells, Btl-GFP mostly accumulated at the cell membrane
GO:0022603 regulation of anatomical structure morphogenesis
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA-predicted regulation of anatomical structure morphogenesis.
Reason: Btl directly executes tracheal branching morphogenesis (captured by GO:0060446 and its children) rather than acting as a regulator of it; the only regulation-type descendant supported is the peripheral negative regulation of axon extension. The generic regulation term over-states the evidence.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0030030 cell projection organization
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted cell projection organization; entailed by filopodium assembly.
Reason: GO:0046847 filopodium assembly (IMP) is accepted elsewhere and entails this term.
Supporting Evidence:
PMID:12015974
Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such
GO:0030517 negative regulation of axon extension
IMP
PMID:17032066
A signaling network for patterning of neuronal connectivity ...
KEEP AS NON CORE
Summary: Btl signalling in dorsal cluster neurons promotes axon retraction, balancing Wnt-driven extension.
Reason: Experimental, full text read; a peripheral neural context of Btl signalling.
Supporting Evidence:
PMID:17032066
blocking the activities of the FGFR Btl [54] or the Rac1 GTPase [50] significantly increased the number of DCN axons crossing between the lobula and the medulla, suggesting that these genes are required for DCN axon retraction
GO:0035008 positive regulation of melanization defense response
IMP
PMID:32396065
A single-cell survey of Drosophila blood.
KEEP AS NON CORE
Summary: btl RNAi in hemocytes reduces melanization of parasitoid wasp eggs.
Reason: acts_upstream_of; real but peripheral immune context.
Supporting Evidence:
PMID:32396065
srp-GAL4-mediated knockdown of btl using two independent RNAi lines (btlRNAi-1 and βˆ’2) reduced the melanization frequency
GO:0035147 branch fusion, open tracheal system
IMP
PMID:12034756
Drosophila tracheal system formation involves FGF-dependent ...
ACCEPT
Summary: FGF-dependent cell extensions contacting bridge-cells are required for dorsal trunk interconnection.
Reason: Part of the Btl-driven tracheal branching program.
Supporting Evidence:
PMID:12034756
the formation of cell extensions require Cdc42-mediated Drosophila fibroblast growth factor activity
GO:0035149 lumen formation, open tracheal system
IGI
PMID:23029159
Drosophila Zpr1 (Zinc finger protein 1) is required downstre...
KEEP AS NON CORE
Summary: Activated Btl drives ectopic lumen formation in terminal cells in a Zpr1-dependent manner.
Reason: Gain-of-function epistasis only; loss of btl could not be tested because btl mutant cells do not branch. Plausible but non-core.
Supporting Evidence:
PMID:23029159
We found that overexpression of this activated form of the FGFR in terminal cells resulted in increased lumen formation as visualized by multiple, gas-filled lumens within single cells
PMID:23029159
We could not directly test loss of FGFR in lumen development because tracheal cells mutant for btl fail to outgrow or undergo branching
GO:0035153 epithelial cell type specification, open tracheal system
IMP
PMID:16760977
Social interactions among epithelial cells during tracheal b...
ACCEPT
Summary: Competition in FGFR activity determines which budding cells take lead (tip) positions.
Reason: Btl activity level specifies tip vs stalk cell identity; core to branch patterning.
Supporting Evidence:
PMID:16760977
those with the highest FGF receptor activity take the lead positions, whereas those with less FGF receptor activity assume subsidiary positions and form the branch stalk
GO:0035154 terminal cell fate specification, open tracheal system
HMP
PMID:21750678
A systematic screen for tube morphogenesis and branching gen...
ACCEPT
Summary: Systematic screen: btl mutant cells are never specified as terminal cells.
Reason: Btl signalling is required for terminal cell specification.
Supporting Evidence:
PMID:21750678
Cells mutant for Breathless FGFR cannot receive the signal, and are relegated to trailing positions, never to be specified a terminal cell.
GO:0035154 terminal cell fate specification, open tracheal system
IMP
PMID:26342211
Ligand-binding and constitutive FGF receptors in single Dros...
ACCEPT
Summary: Terminal cell fate specification depends on Btl activity.
Reason: Consistent with classic data that quantitative Btl activity sets terminal branching fates.
Supporting Evidence:
PMID:8918892
spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
GO:0035202 tracheal pit formation in open tracheal system
IMP
PMID:16818611
The RhoGAP crossveinless-c links trachealess and EGFR signal...
UNDECIDED
Summary: IMP annotation to tracheal pit formation from a study of Crossveinless-c and EGFR in tracheal invagination.
Reason: Abstract-only; the abstract attributes invagination to Trachealess and EGFR, and older data state that tracheal pits form in deletions removing btl. Cannot verify what the curator saw in the full text, so not removed.
Supporting Evidence:
PMID:16818611
whose specific transcriptional activation in the tracheal cells is triggered by both the trachealess patterning gene and the EGF Receptor (EGFR) signaling pathway
PMID:1849109
In embryos homozygous for a deletion of several genes including the DFGF-R locus, the initial formation of the tracheal pits is not affected.
GO:0035215 genital disc development
IEP
PMID:12062107
Sex-specific deployment of FGF signaling in Drosophila recru...
KEEP AS NON CORE
Summary: FGF recruits receptor-expressing mesodermal cells into the male genital disc.
Reason: IEP-type evidence; plausible peripheral role.
Supporting Evidence:
PMID:12062107
Drosophila FGF is used, only in males, to recruit mesodermal cells expressing its receptor to become part of the genital imaginal disc
GO:0035230 cytoneme
IDA
PMID:21493861
Specificity of Drosophila cytonemes for distinct signaling p...
ACCEPT
Summary: Btl is present on air sac primordium cytonemes that contact Bnl-producing wing disc cells.
Reason: Cytonemes are a ligand-receiving location for Btl; several independent imaging studies agree.
Supporting Evidence:
PMID:21493861
Each ASP had only a few long (>30 ΞΌm) cytonemes, most of which contained Btl:Cherry puncta.
GO:0035230 cytoneme
IDA
PMID:24385607
Cytoneme-mediated contact-dependent transport of the Drosoph...
ACCEPT
Summary: Btl is present on air sac primordium cytonemes that contact Bnl-producing wing disc cells.
Reason: Cytonemes are a ligand-receiving location for Btl; several independent imaging studies agree.
Supporting Evidence:
PMID:24385607
Cells at the ASP tip extend long (β‰₯30 ΞΌm) cytonemes that contain the FGF receptor Breathless (FGFR) and appear to touch FGF-producing disc cells.
GO:0035230 cytoneme
IDA
PMID:30328809
Feedback regulation of cytoneme-mediated transport shapes a ...
ACCEPT
Summary: Btl is present on air sac primordium cytonemes that contact Bnl-producing wing disc cells.
Reason: Cytonemes are a ligand-receiving location for Btl; several independent imaging studies agree.
Supporting Evidence:
PMID:30328809
Densely packed Btl:Cherry molecules were visualized on the surface of the ASP cytonemes
GO:0042690 negative regulation of crystal cell differentiation
IMP
PMID:33395389
The vascular niche controls Drosophila hematopoiesis via fib...
KEEP AS NON CORE
Summary: btl knockdown in lymph gland progenitors increases crystal cell differentiation, rescued by activated Btl.
Reason: Peripheral (hematopoietic niche) context.
Supporting Evidence:
PMID:33395389
Crystal cell numbers increase when btl is knocked down in progenitors (e) and crystal cell differentiation is rescued when a constitutive activated btl receptor (btlCA) is expressed in the btl-RNAi context (f).
GO:0043235 signaling receptor complex
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: IBA: RTK family receptor complex.
Reason: Btl forms a complex with the adaptor Dof upon activation; plausible but not the defining feature.
Supporting Evidence:
PMID:15082772
full-length Dof or the minimal Dof600 protein formed a complex with the activated version of both Drosophila FGFRs upon induction
GO:0043410 positive regulation of MAPK cascade
IBA
GO_REF:0000033
ACCEPT
Summary: IBA: FGFR/RTK activation of the MAPK cascade.
Reason: Bnl/Btl signalling activates MAPK through Dof, Hbr, Csw and Src64B; well supported in Drosophila.
Supporting Evidence:
PMID:12175485
Branchless/Breathless signaling activates MAP-kinase, which in turn, activates late btl expression
PMID:9778498
heartbroken is involved in both the HEARTLESS- and BREATHLESS-dependent activation of MAPK
GO:0045614 negative regulation of plasmatocyte differentiation
IMP
PMID:33395389
The vascular niche controls Drosophila hematopoiesis via fib...
KEEP AS NON CORE
Summary: btl knockdown in progenitors increases plasmatocyte numbers.
Reason: Peripheral hematopoietic context.
Supporting Evidence:
PMID:33395389
An increase in plasmatocyte number (labeled by P1 antibodies, green) is observed when btl expression is decreased in progenitors (k) compared to the control (j).
GO:0045887 positive regulation of synaptic assembly at neuromuscular junction
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA-predicted positive regulation of NMJ synaptic assembly.
Reason: Only evidence is a dominant genetic modifier effect in a Smn-knockdown background; btl/+ has no NMJ effect alone.
Supporting Evidence:
PMID:21300852
how24BGAL4; btldev1/+ animals do not show any significant effects on the NMJ.
GO:0045887 positive regulation of synaptic assembly at neuromuscular junction
IGI
PMID:21300852
Modeling spinal muscular atrophy in Drosophila links Smn to ...
MARK AS OVER ANNOTATED
Summary: btl heterozygosity enhances the NMJ defects of muscle Smn knockdown.
Reason: Full text read: btl/+ alone has no NMJ phenotype; the interaction is in a sensitized background and the tissue in which Btl would act is not established. Weak support for a direct role in synapse assembly.
Supporting Evidence:
PMID:21300852
how24BGAL4; btldev1/+ animals do not show any significant effects on the NMJ.
PMID:21300852
these heterozygous FGF receptor mutations elicited a drastic decrease in synaptic size when compared with loss of Smn alone
GO:0046847 filopodium assembly
IMP
PMID:12015974
In vivo imaging reveals different cellular functions for FGF...
ACCEPT
Summary: Bnl/Btl signalling controls dynamic filopodia formation in tracheal tip cells.
Reason: Direct cellular output of Btl signalling underlying chemotactic migration.
Supporting Evidence:
PMID:12015974
Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such
GO:0048468 cell development
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted cell development; true but generic.
Reason: Entailed by specific experimentally supported terms kept in this review (tracheal branching, tracheal epithelial cell migration, border follicle cell migration, compound eye morphogenesis, lumen formation).
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0048513 animal organ development
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted animal organ development; true but generic.
Reason: Entailed by specific experimentally supported terms kept in this review (tracheal branching, tracheal epithelial cell migration, border follicle cell migration, compound eye morphogenesis, lumen formation).
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0048646 anatomical structure formation involved in morphogenesis
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted anatomical structure formation involved in morphogenesis; true but generic.
Reason: Entailed by specific experimentally supported terms kept in this review (tracheal branching, tracheal epithelial cell migration, border follicle cell migration, compound eye morphogenesis, lumen formation).
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0048729 tissue morphogenesis
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted tissue morphogenesis; true but generic.
Reason: Entailed by specific experimentally supported terms kept in this review (tracheal branching, tracheal epithelial cell migration, border follicle cell migration, compound eye morphogenesis, lumen formation).
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
GO:0060438 trachea development
IMP
PMID:19285057
Regulation of Drosophila embryonic tracheogenesis by dVHL an...
MODIFY
Summary: dVHL tracheal phenotypes are suppressed by removing a copy of btl.
Reason: GO:0060438 trachea development is the vertebrate airway term (portion of the airway attaching to the bronchi); the insect structure is GO:0007424 open tracheal system development, which btl already carries.
Proposed replacements: open tracheal system development
Supporting Evidence:
PMID:19285057
Loss of one copy of either btl or bnl led to a significant reduction in the penetrance of dVHLi34B3 tracheal phenotypes
GO:0060446 branching involved in open tracheal system development
IDA
PMID:30328809
Feedback regulation of cytoneme-mediated transport shapes a ...
ACCEPT
Summary: Endogenous Btl binds Bnl in the ASP and shapes the receptor-bound gradient controlling branching.
Reason: Core process.
Supporting Evidence:
PMID:30328809
In trans-heterozygous btl:cherryendo/bnl:gfpendo animals, all the Bnl:GFP puncta in the ASP colocalized with Btl:Cherry and the receptor gradient coincided with that of the ligand gradient
GO:0060446 branching involved in open tracheal system development
IMP
PMID:21750259
A novel function for the PAR complex in subcellular morphoge...
ACCEPT
Summary: Activated Btl increases terminal cell branching, dependent on PAR complex.
Reason: Core process.
Supporting Evidence:
PMID:21750259
We expressed Ξ»Btl in individual terminal cells and found that this leads to an increase in branch number, as well as cell growth
GO:0090130 tissue migration
IEA
GO_REF:0000117
TOO GENERAL
Summary: ARBA-predicted tissue migration; true but generic.
Reason: Entailed by specific experimentally supported terms kept in this review (tracheal branching, tracheal epithelial cell migration, border follicle cell migration, compound eye morphogenesis, lumen formation).
Supporting Evidence:
PMID:1325393
The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.

Core Functions

Branchless-activated FGF receptor tyrosine kinase at the plasma membrane and on cytonemes; signals via the adaptor Dof to Ras/MAPK.

Supporting Evidence:
  • PMID:8978613
    bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase
  • PMID:15082772
    expression of constitutive active Btl or Htl led to strong tyrosine phosphorylation of Dof
  • PMID:30328809
    In trans-heterozygous btl:cherryendo/bnl:gfpendo animals, all the Bnl:GFP puncta in the ASP colocalized with Btl:Cherry

Directs chemotactic migration of tracheal epithelial cells toward Bnl sources, driving primary branch outgrowth and tracheal branching morphogenesis.

Supporting Evidence:
  • PMID:1325393
    The tracheal cells fail to migrate in severe mutants and remain within the tracheal pits.
  • PMID:26342211
    FGF can act as a chemoattractant rather than as a motogen in collective cell migration

Graded Btl activity selects tip cells and specifies secondary and terminal branch cell fates in the tracheal system.

Supporting Evidence:
  • PMID:8918892
    quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates
  • PMID:16760977
    those with the highest FGF receptor activity take the lead positions

References

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Suggested Questions for Experts

Q: Does Btl bind Branchless directly with measurable affinity, and do heparan sulfate proteoglycans act as co-receptors as for vertebrate FGFRs?

Q: Does Btl act directly in larval muscle or motor neurons to support NMJ growth, or is the Smn genetic interaction indirect?

Q: Is Btl required for tracheal invagination (pit formation), or is that step entirely EGFR/Trachealess-dependent?

Suggested Experiments

Experiment: Measure direct Bnl-Btl ectodomain binding (SPR or cell-based binding) with and without heparan sulfate, to support an FGF binding annotation.

Experiment: Use conditional (temperature-sensitive or degron) btl alleles after primary branching to test loss of function in terminal cell lumen formation, complementing the gain-of-function Zpr1 epistasis.

Deep Research

FlyBase

(btl-deep-research-flybase.md)
FlyBase gene description for btl (DROME) FlyBase

FlyBase gene description for btl (DROME)

breathless (btl) encodes a Fibroblast Growth Factor (FGF) receptor for secreted FGF ligands that utilizes the intracellular Ras-MAP kinase pathway. It contributes to embryonic tracheal migration.

Manual

(btl-deep-research-manual.md)

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πŸ“š Additional Documentation

Notes

(btl-notes.md)

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πŸ“„ View Raw YAML

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