Receptor tyrosine phosphatases control tracheal tube geometries through negative regulation of Egfr signaling
- Creators
- Jeon, Mili
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Zinn, Kai
Abstract
The formation of epithelial tubes with defined shapes and sizes is essential for organ development. We describe a unique tracheal tubulogenesis phenotype caused by loss of both Drosophila type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. Ptp4E is the only widely expressed Drosophila RPTP, and is the last of the six fly RPTPs to be genetically characterized. We recently isolated mutations in Ptp4E, and discovered that, although Ptp4E null mutants have no detectable phenotypes, double mutants lacking both Ptp4E and Ptp10D display synthetic lethality at hatching owing to respiratory failure. In these double mutants, unicellular and terminal tracheal branches develop large bubble-like cysts that selectively incorporate apical cell surface markers. Cysts in unicellular branches are enlargements of the lumen that are sealed by adherens junctions, whereas cysts in terminal branches are cytoplasmic vacuoles. Cyst size and number are increased by tracheal expression of activated Egfr tyrosine kinase, and decreased by reducing Egfr levels. Ptp10D forms a complex with Egfr in transfected cells. Downregulation of Egfr signaling by the RPTPs is required for the construction of tubular lumens, whether extracellular or intracellular, by cells that undergo remodeling during branch morphogenesis. The Ptp4E Ptp10D phenotype represents the first evidence of an essential role for RPTPs in epithelial organ development. These findings might be relevant to organ development and disease in mammals, because PTPRJ (DEP-1), an ortholog of Ptp4E/Ptp10D, interacts with the hepatocyte growth factor receptor tyrosine kinase. PTPRJ corresponds to the murine Scc1 (suppressor of colon cancer) gene.
Additional Information
© The Company of Biologists Ltd 2009. Accepted 2 July 2009. First published online 12 August 2009 doi: 10.1242/dev.033597 We thank Amin Ghabrial, Mark Krasnow, Sandra Schmid, Keith Mostov, Volker Hartenstein and members of the Zinn group for helpful discussions. We also thank Rosalind Young for help with TEM experiments; Alasdair McDowall and the Caltech EM Center for technical support; and Adam Friedman for help with mtDer cell culture. We also thank the Schuman lab for use of their confocal microscope, and Matthew Scott (Stanford) for providing laboratory space used for part of this work. This work was supported by an NIH RO1 grant (NS28182) to K.Z. Deposited in PMC for release after 12 months. Supplementary material for this article is available at http://dev.biologists.org/cgi/content/full/136/18/3121/DC1Attached Files
Supplemental Material - Jeon033597-FigS1.jpg
Supplemental Material - Jeon033597-FigS2.jpg
Supplemental Material - Jeon033597-FigS3.jpg
Supplemental Material - Jeon033597-FigS4.jpg
Supplemental Material - Jeon033597-FigS5.jpg
Supplemental Material - Jeon2009p5843Development.pdf
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Additional details
- PMCID
- PMC2730367
- Eprint ID
- 15658
- Resolver ID
- CaltechAUTHORS:20090908-083706162
- RO1 NS28182
- NIH
- Created
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2009-09-22Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field