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 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.
Shraiman
Boris I
BI
Kavli Institute for Theoretical Physics, Kohn Hall, University of California, Santa Barbara, CA 93106, USA. shraiman@kitp.ucsb.edu
D000818:Animals; D004330:Drosophila / Q000254:growth & development*; D005246:Feedback
Curr Biol. 1997 Mar 1;7(3):R186-95
9162486
Nature. 2004 May 6;429(6987):83-6
15103386
Cell. 1996 Nov 29;87(5):833-44
8945511
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7502-7
12032312
Results Probl Cell Differ. 1978;9:97-118
373042
Development. 1995 Aug;121(8):2265-78
7671794
Dev Cell. 2004 Jul;7(1):85-93
15239956
Dev Biol. 1996 Dec 15;180(2):377-88
8954711
Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jun;65(6 Pt 1):061914
12188766
Nature. 2002 Apr 18;416(6882):755-9
11961558
Biochem Biophys Res Commun. 2001 Aug 3;285(5):1077-83
11478763
Cell. 2004 Apr 2;117(1):117-29
15066287
Curr Opin Cell Biol. 1999 Oct;11(5):554-60
10508659
Cell. 2001 Sep 21;106(6):785-94
11572783
Development. 1996 Jul;122(7):2261-9
8681806
In Vitro Cell Dev Biol Anim. 1999 Sep;35(8):441-8
10501083
Development. 2002 Feb;129(4):1003-13
11861483
J Cell Biol. 2001 Jun 11;153(6):1175-86
11402062
Dev Biol. 2002 Nov 1;251(1):74-90
12413899
Physiol Rev. 2001 Apr;81(2):685-740
11274342
Cell. 2003 Jan 24;112(2):147-50
12553903
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):640-5
8570608
Bioessays. 2002 Jan;24(1):54-64
11782950
Nat Cell Biol. 2002 Apr;4(4):E101-8
11944044
Curr Biol. 2003 Aug 19;13(16):1365-77
12932320
J Cell Biol. 1996 Jul;134(1):133-48
8698810
Dev Biol. 1975 Feb;42(2):211-21
1116643
J Cell Biol. 2001 Oct 29;155(3):427-38
11673478
Cell. 1999 Jan 22;96(2):235-44
9988218
Dev Cell. 2002 Jun;2(6):797-805
12062091
Nature. 2001 Sep 13;413(6852):194-202
11557988
Int J Dev Biol. 1998;42(3):353-62
9654019
Development. 2000 Jul;127(14):2977-87
10862736
Development. 1997 Feb;124(4):871-80
9043068
Nature. 1996 May 30;381(6581):387-93
8632795
Nat Rev Mol Cell Biol. 2004 Oct;5(10):805-15
15459661
Trends Cell Biol. 1995 Jun;5(6):224-9
14732126
Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9467-71
10944216
Dev Biol. 1997 Jan 15;181(2):246-56
9013934
Cell. 1996 May 3;85(3):357-68
8616891
Phys Rev Lett. 2000 May 1;84(18):4244-7
10990656
Nature. 2003 Mar 13;422(6928):161-3
12634785
Curr Opin Oncol. 1998 Jan;10(1):81-7
9466489
Biophys J. 1998 May;74(5):2227-34
9591650
J Math Biol. 1980 May;9(3):291-5
7190180
Annu Rev Cell Dev Biol. 2003;19:677-95
14570586
Cell. 2004 Apr 2;117(1):107-16
15066286
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4728-35
14960734
Dev Biol. 1981 Jul 30;85(2):299-308
7262460