title: Function of the Drosophila POU domain transcription factor drifter as an upstream regulator of breathless receptor tyrosine kinase expression in developing trachea.
abstract: Organogenesis of the Drosophila tracheal system involves extensive directed cell migrations leading to a stereotypic series of interconnected tubules. Although numerous gene products have been shown to be essential for tracheal morphogenesis, direct functional relationships between participants have not been previously established. Both the breathless gene, encoding a Drosophila fibroblast growth factor receptor tyrosine kinase homologue, and the POU-domain transcription factor gene, drifter, are expressed in all tracheal cells and are essential for directed cell migrations. We demonstrate here that ubiquitously expressed Breathless protein under control of a heterologous heat-shock promoter is able to rescue the severely disrupted tracheal phenotype associated with drifter loss-of-function mutations. In the absence of Drifter function, breathless expression is initiated normally but transcript levels fall drastically to undetectable levels as tracheal differentiation proceeds. In addition, breathless regulatory DNA contains seven high affinity Drifter binding sites similar to previously identified Drifter recognition elements. These results suggest that the Drifter protein, which maintains its own expression through a tracheal-specific autoregulatory enhancer, is not necessary for initiation of breathless expression but functions as a direct transcriptional regulator necessary for maintenance of breathless transcripts at high levels during tracheal cell migration. This example of a mechanism for maintenance of a committed cell fate offers a model for understanding how essential gene activities can be maintained throughout organogenesis.
authors.affiliation: Department of Physiology and Biophysics, University of Iowa, College of Medicine, Iowa City 52242, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Anderson
authors.forename: S J
authors.initials: SJ
authors.lastname: Certel
authors.forename: K
authors.initials: K
authors.lastname: Certel
authors.forename: T
authors.initials: T
authors.lastname: Lee
authors.forename: D J
authors.initials: DJ
authors.lastname: Montell
authors.forename: W A
authors.initials: WA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001665:Binding Sites; D019521:Body Patterning; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D009024:Morphogenesis; D009154:Mutation; D050809:POU Domain Factors; D010641:Phenotype; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D012045:Regulatory Sequences, Nucleic Acid; D014018:Tissue Distribution; D014132:Trachea / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050809:POU Domain Factors; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; C091575:vvl protein, Drosophila; C102301:BTL protein, Drosophila; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases