title: The bHLH transcription factor, hairy, refines the terminal cell fate in the Drosophila embryonic trachea.
abstract: BACKGROUND
  The pair-rule gene, hairy, encodes a basic helix-loop-helix transcription factor and is required for patterning of the early Drosophila embryo and for morphogenesis of the embryonic salivary gland. Although hairy was shown to be expressed in the tracheal primordia and in surrounding mesoderm, whether hairy plays a role in tracheal development is not known.
  
  
  RESULTS
  Here, we report that hairy is required for refining the terminal cell fate in the embryonic trachea and that hairy's tracheal function is distinct from its earlier role in embryonic patterning. In hairy mutant embryos where the repressive activity of hairy is lost due to lack of its co-repressor binding site, extra terminal cells are specified in the dorsal branches. We show that hairy functions in the muscle to refine the terminal cell fate to a single cell at the tip of the dorsal branch by limiting the expression domain of branchless (bnl), encoding the FGF ligand, in surrounding muscle cells. Abnormal activation of the Bnl signaling pathway in hairy mutant tracheal cells is exemplified by increased number of dorsal branch cells expressing Bnl receptor, Breathless (Btl) and Pointed, a downstream target of the Bnl/Btl signaling pathway. We also show that hairy genetically interacts with bnl in TC fate restriction and that overexpression of bnl in a subset of the muscle surrounding tracheal cells phenocopied the hairy mutant phenotype.
  
  
  CONCLUSIONS
  Our studies demonstrate a novel role for Hairy in restriction of the terminal cell fate by limiting the domain of bnl expression in surrounding muscle cells such that only a single dorsal branch cell becomes specified as a terminal cell. These studies provide the first evidence for Hairy in regulation of the FGF signaling pathway during branching morphogenesis.
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York, United States of America.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Zhan
authors.forename: Saw W
authors.initials: SW
authors.lastname: Maung
authors.forename: Bing
authors.initials: B
authors.lastname: Shao
authors.forename: Monn Monn
authors.initials: MM
authors.lastname: Myat
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics*; D009132:Muscles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D014132:Trachea / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005346:Fibroblast Growth Factors; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D012097:Repressor Proteins; D014157:Transcription Factors; C102644:bnl protein, Drosophila; C083884:pnt protein, Drosophila; C061841:hairy protein, insect; C102301:BTL protein, Drosophila