title: The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size.
abstract: Tubes with distinct shapes and sizes are critical for the proper function of many tubular organs. Here we describe a unique phenotype caused by the loss of a novel, evolutionarily-conserved, Drosophila Smad-like protein, Expansion. In expansion mutants, unicellular and intracellular tracheal branches develop bubble-like cysts with enlarged apical membranes. Cysts in unicellular tubes are enlargements of the apical lumen, whereas cysts in intracellular tubes are cytoplasmic vacuole-like compartments. The cyst phenotype in expansion mutants is similar to, but weaker than, that observed in double mutants of Drosophila type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. Ptp4E and Ptp10D negatively regulate the receptor tyrosine kinase (RTK) pathways, especially epithelial growth factor receptor (EGFR) and fibroblast growth factor receptor/breathless (FGFR, Btl) signaling to maintain the proper size of unicellular and intracellular tubes. We show Exp genetically interacts with RTK signaling, the downstream targets of RPTPs. Cyst size and number in expansion mutants is enhanced by increased RTK signaling and suppressed by reduced RTK signaling. Genetic interaction studies strongly suggest that Exp negatively regulates RTK (EGFR, Btl) signaling to ensure proper tube sizes. Smad proteins generally function as intermediate components of the transforming growth factor-β (TGF-β, DPP) signaling pathway. However, no obvious genetic interaction between expansion and TGF-β (DPP) signaling was observed. Therefore, Expansion does not function as a typical Smad protein. The expansion phenotype demonstrates a novel role for Smad-like proteins in epithelial tube formation.
authors: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
authors: Ekaterini
authors: E
authors: Iordanou
authors: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
authors: Rachana R
authors: RR
authors: Chandran
authors: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
authors: Yonghua
authors: Y
authors: Yang
authors: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
authors: Mina
authors: M
authors: Essak
authors: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
authors: Nicholas
authors: N
authors: Blackstone
authors: Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA. Electronic address: Jiang23@oakland.edu.
authors: Lan
authors: L
authors: Jiang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000502:physiology*; D014132:Trachea / Q000033:anatomy & histology / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D017468:Receptors, Fibroblast Growth Factor; D018010:Receptors, Invertebrate Peptide; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; C000592845:exp protein, Drosophila; C102301:BTL protein, Drosophila; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; C519388:Ptp10D protein, Drosophila; C533524:Ptp4E protein, Drosophila; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4
keywords: Cyst; Expansion; Map kinase; RTK; Rho; Smad; Tracheal