Requirement for chitin biosynthesis in epithelial tube morphogenesis

Many organs are composed of branched networks of epithelial tubes that transport vital fluids or gases. The proper size and shape of tubes are crucial for their transport function, but the molecular processes that govern tube size and shape are not well understood. Here we show that three genes requ...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 47; pp. 17014 - 17019
Main Authors: Devine, W.P, Lubarsky, B, Shaw, K, Luschnig, S, Messina, L, Krasnow, M.A
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 22-11-2005
National Acad Sciences
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Summary:Many organs are composed of branched networks of epithelial tubes that transport vital fluids or gases. The proper size and shape of tubes are crucial for their transport function, but the molecular processes that govern tube size and shape are not well understood. Here we show that three genes required for tracheal tube morphogenesis in Drosophila melanogaster encode proteins involved in the synthesis and accumulation of chitin, a polymer of N-acetyl-β-D-glucosamine that serves as a scaffold in the rigid extracellular matrix of insect cuticle. In all three mutants, developing tracheal tubes bud and extend normally, but the epithelial walls of the tubes do not expand uniformly, and the resultant tubes are grossly misshapen, with constricted and distended regions all along their lengths. The genes are expressed in tracheal cells during the expansion process, and chitin accumulates in the lumen of tubes, forming an expanding cylinder that we propose coordinates the behavior of the surrounding tracheal cells and stabilizes the expanding epithelium. These findings show that chitin regulates epithelial tube morphogenesis, in addition to its classical role protecting mature epithelia.
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To whom correspondence should be addressed. E-mail: krasnow@cmgm.stanford.edu.
Edited by Kathryn V. Anderson, Sloan-Kettering Institute, New York, NY
Abbreviations: SNP, single-nucleotide polymorphism; TEM, transmission electron microscopy.
Author contributions: W.P.D., B.L., K.S., S.L., L.M., and M.A.K. designed research; W.P.D., B.L., K.S., S.L., and L.M. performed research; W.P.D., B.L., K.S., S.L., L.M., and M.A.K. analyzed data; and W.P.D., B.L., K.S., S.L., and M.A.K. wrote the paper.
W.P.D., B.L., and K.S. contributed equally to this work.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Present address: Lehrstuhl für Genetik, Universität Bayreuth, D-95447 Bayreuth, Germany.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0506676102