The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size.

Ekaterini Iordanou, Rachana R Chandran, Yonghua Yang, Mina Essak, Nicholas Blackstone, Lan Jiang

Developmental biology 2014 Sep 01

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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. Copyright © 2014 Elsevier Inc. All rights reserved.

Citation

Ekaterini Iordanou, Rachana R Chandran, Yonghua Yang, Mina Essak, Nicholas Blackstone, Lan Jiang. The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size. Developmental biology. 2014 Sep 01;393(1):93-108