Mechanical Feedback as a Possible Regulator of Tissue Growth

Regulation of cell growth and proliferation has a fundamental role in animal and plant development and in the progression of cancer. In the context of development, it is important to understand the mechanisms that coordinate growth and patterning of tissues. Imaginal discs, which are larval precurso...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-03, Vol.102 (9), p.3318-3323
Main Authors: Shraiman, Boris I., Wieschaus, Eric F.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Sciences
Cell division
Cell growth
Deformation
Drosophila - growth & development
Elastic tissue
Embryonic cells
Endothelial cells
Feedback
Imaginal discs
Insects
Mathematical growth
Mathematical models
Mechanical stress
Physical growth
Scientific apparatus & instruments
Tissues
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Summary:Regulation of cell growth and proliferation has a fundamental role in animal and plant development and in the progression of cancer. In the context of development, it is important to understand the mechanisms that coordinate growth and patterning of tissues. Imaginal discs, which are larval precursors of fly limbs and organs, have provided much of what we currently know about these processes. Here, we consider the mechanism that is responsible for the observed uniformity of growth in wing imaginal discs, which persists in the presence of gradients in growth inducing morphogens in spite of the stochastic nature of cell division. The phenomenon of "cell competition," which manifests in apoptosis of slower-growing cells in the vicinity of faster growing tissue, suggests that uniform growth is not a default state but a result of active regulation. How can a patch of tissue compare its growth rate with that of its surroundings? A possible way is furnished by mechanical interactions. To demonstrate this mechanism, we formulate a mathematical model of nonuniform growth in a layer of tissue and examine its mechanical implications. We show that a clone growing faster or slower than the surrounding tissue is subject to mechanical stress, and we propose that dependence of the rate of cell division on local stress could provide an "integral-feedback" mechanism stabilizing uniform growth. The proposed mechanism of growth control is not specific to imaginal disc growth and could be of general relevance. Several experimental tests of the proposed mechanism are suggested.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0404782102