title: Integration of an abdominal Hox complex with Pax2 yields cell-specific EGF secretion from Drosophila sensory precursor cells.
abstract: Cis-regulatory modules (CRMs) ensure specific developmental outcomes by mediating both proper spatiotemporal gene expression patterns and appropriate transcriptional levels. In Drosophila, the precise transcriptional control of the serine protease rhomboid regulates EGF signaling to specify distinct cell types. Recently, we identified a CRM that activates rhomboid expression and thereby EGF secretion from a subset of abdominal sensory organ precursor cells (SOPs) to induce an appropriate number of lipid-processing cells called oenocytes. Here, we use scanning mutagenesis coupled with reporter assays, biochemistry and genetics to dissect the transcriptional mechanisms regulating SOP-specific rhomboid activation. Our results show that proper spatial activity of the rhomboid CRM is dependent upon direct integration of the abdomen-specific Hox factor Abdominal-A and the SOP-restricted Pax2 factor. In addition, we show that the Extradenticle and Homothorax Hox co-factors are differentially integrated on the rhomboid CRM by abdominal versus thoracic Hox proteins in the presence of Pax2. Last, we show that Abdominal-A uses both Pax2-dependent and Pax2-independent mechanisms to stimulate rhomboid CRM activity to induce proper oenocyte numbers. Thus, these data demonstrate how a CRM integrates Hox and neural transcriptional inputs to regulate the appropriate spatial pattern and levels of EGF secretion to specify an essential cell fate.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital, 3333 Burnet Avenue, MLC 7007, Cincinnati, OH 45229, USA.
authors.forename: David
authors.initials: D
authors.lastname: Li-Kroeger
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Cook
authors.forename: Brian
authors.initials: B
authors.lastname: Gebelein
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004815:Epidermal Growth Factor / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D008156:Luciferases; D008565:Membrane Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D016296:Mutagenesis; D058953:Neural Stem Cells / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C410542:Abd-A protein, insect; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D051762:PAX2 Transcription Factor; C081481:Rho protein, Drosophila; D014157:Transcription Factors; C083405:exd protein, Drosophila; C108704:hth protein, Drosophila; D004815:Epidermal Growth Factor; D008156:Luciferases