Abstract
Networks of epithelial and endothelial tubes are essential for the function of organs such as the lung, kidney and vascular system. The sizes and shapes of these tubes are highly regulated to match their individual functions. Defects in tube size can cause debilitating diseases such as polycystic kidney disease and ischaemia. It is therefore critical to understand how tube dimensions are regulated. Here we identify the tyrosine kinase Src as an instructive regulator of epithelial-tube length in the Drosophila tracheal system. Loss-of-function Src42 mutations shorten tracheal tubes, whereas Src42 overexpression elongates them. Surprisingly, Src42 acts distinctly from known tube-size pathways and regulates both the amount of apical surface growth and, with the conserved formin dDaam, the direction of growth. Quantitative three-dimensional image analysis reveals that Src42-and dDaam-mutant tracheal cells expand more in the circumferential than the axial dimension, resulting in tubes that are shorter in length-but larger in diameter-than wild-type tubes. Thus, Src42 and dDaam control tube dimensions by regulating the direction of anisotropic growth, a mechanism that has not previously been described.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 518-525 |
| Number of pages | 8 |
| Journal | Nature Cell Biology |
| Volume | 14 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2012 |
Funding
We thank M. Zeeb and E. Lammert for sharing unpublished results and comments on the manuscript, R. Carthew, S. Hilgenfeldt and A. Dudley for discussions, Bill Russin and the Northwestern Biological Imaging Facility for imaging support, S. Hayashi, A. O’Reilly, T. Xu, the Bloomington Stock Center and the Developmental Studies Hybridoma Bank for fly stocks and reagents, M. Singh for technical advice and R. Robbins, T. Helenius and T. Krupinski for comments on the manuscript. This work was supported by a predoctoral fellowship from the National Institutes of Health (NIH) Cellular and Molecular Basis of Disease training grant (T32 GM008061 to K.S.N.), a Malkin Scholar Award (to K.S.N.), an Achievement Rewards for College Scientists (ARCS) Award (to K.S.N.), a grant from the Northwestern University Alumni Association (to G.J.B.), NIH grant P50 GM 071508, principal investigator D. Botstein (Z.K. and M.K.), and Hungarian Scientific Research Fund (OTKA) grant K 82039 (to J.M.).
ASJC Scopus subject areas
- Cell Biology