title: Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system.
abstract: Receptor tyrosine kinases (RTKs) are members of a diverse class of signaling molecules well known for their roles in cell fate specification, cell differentiation, and oncogenic transformation. Recently several RTKs have been implicated in cell and axon motility, and RTKs are known to mediate chemotactic guidance of tissue culture cells. 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. We found that expression of a constitutively active receptor during tracheal development interfered with directed tracheal cell migration and led to extra secondary and terminal branch-forming cells. Reduction in endogenous BTL signaling enhanced the cell migration defects while suppressing the ectopic branching defects. These results are consistent with a model for tracheal development in which spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205-2185, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lee
authors.forename: N
authors.initials: N
authors.lastname: Hacohen
authors.forename: M
authors.initials: M
authors.lastname: Krasnow
authors.forename: D J
authors.initials: DJ
authors.lastname: Montell
mesh_terms: D000818:Animals; D002465:Cell Movement; D004330:Drosophila / Q000033:anatomy & histology / Q000196:embryology*; D029721:Drosophila Proteins; D004789:Enzyme Activation; D015870:Gene Expression; D018869:Heat-Shock Response; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000502:physiology*; D009024:Morphogenesis; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D012137:Respiratory System / Q000033:anatomy & histology / Q000196:embryology*
chemical_list: D029721:Drosophila Proteins; D019476:Insect Proteins; D017468:Receptors, Fibroblast Growth Factor; C102301:BTL protein, Drosophila; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases