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On the growth and form of the gut


The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut.

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Figure 1: Morphology of loops in the chick gut.
Figure 2: Rubber simulacrum of gut looping morphogenesis.
Figure 3: Geometric and mechanical measurements of chick gut.
Figure 4: Predictions for loop shape, size and number at three stages in chick gut development.
Figure 5: Comparative predictions for looping parameters across species.

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  1. His, W. Anatomie Menschlicher Embryonen (Vogel, 1880)

    Book  Google Scholar 

  2. Thompson, D. W. On Growth and Form (Cambridge Univ. Press, 1917)

    Google Scholar 

  3. Johnson, R. L. & Tabin, C. J. Molecular models for vertebrate limb development. Cell 90, 979–990 (1997)

    Article  CAS  Google Scholar 

  4. Metzger, R. J. & Krasnow, M. A. Genetic control of branching morphogenesis. Science 284, 1635–1639 (1999)

    Article  CAS  Google Scholar 

  5. Hufnagel, L. et al. On the mechanism of wing size determination in fly development. Proc. Natl Acad. Sci. USA 104, 3835–3840 (2007)

    Article  ADS  CAS  Google Scholar 

  6. Beloussov, L. V. et al. Mechanical stresses in embryonic tissues: patterns, morphogenetic role, and involvement in regulatory feedback. Int. Rev. Cytol. 150, 1–34 (1994)

    Article  CAS  Google Scholar 

  7. Taber, L. A. Biomechanics of cardiovascular development. Annu. Rev. Biomed. Eng. 3, 1–25 (2001)

    Article  CAS  Google Scholar 

  8. Salazar-Ciudad, I. & Jernvall, J. A computational model of teeth and the developmental origins of morphological variation. Nature 464, 583–586 (2010)

    Article  ADS  CAS  Google Scholar 

  9. Hamant, O. et al. Developmental patterning by mechanical signals in Arabidopsis . Science 322, 1650–1655 (2008)

    Article  ADS  CAS  Google Scholar 

  10. Forgacs, G. & Newman, S. Biological Physics of the Developing Embryo (Cambridge Univ. Press, 2005)

    Book  Google Scholar 

  11. Schoenwolf, G. et al. Larsen’s Human Embryology Ch. 14 (Elsevier Health Sciences, 2008)

    Google Scholar 

  12. Kurpios, N. A. et al. The direction of gut looping is established by changes in the extracellular matrix and in cell:cell adhesion. Proc. Natl Acad. Sci. USA 105, 8499–8506 (2008)

    Article  ADS  CAS  Google Scholar 

  13. Davis, N. M. et al. The chirality of gut rotation derives from left-right asymmetric changes in the architecture of the dorsal mesentery. Dev. Cell 15, 134–145 (2008)

    Article  CAS  Google Scholar 

  14. Hecksher-Sorensen, J. et al. The splanchnic mesodermal plate directs spleen and pancreatic laterality, and is regulated by Bapx1/Nkx3. 2 . Development 131, 4665–4675 (2004)

    Article  CAS  Google Scholar 

  15. Kleinman, R. E. et al. Walker’s Pediatric Gastrointestinal Disease 207–216 (Decker, 2008)

    Google Scholar 

  16. Fung, Y. C. Biomechanics: Mechanical Properties of Living Tissues 2nd edn, 242–320 (Springer, 2004)

    Google Scholar 

  17. Liang, H. & Mahadevan, L. The shape of a long leaf. Proc. Natl Acad. Sci. USA 106, 22049–22054 (2009)

    Article  ADS  MathSciNet  CAS  Google Scholar 

  18. Beddard, F. E. The Structure and Classification of Birds (Longmans, Green and Co., 1898)

    Book  Google Scholar 

  19. Mitchell, C. P. On the intestinal tract of birds. Proc. Zool. Soc. Lond. 64, 136–159 (1896)

    Article  Google Scholar 

  20. Hamburger, H. & Hamilton, H. L. A series of normal stages in the development of the chick embryo. J. Exp. Morphol. 88, 49–92 (1951)

    Article  CAS  Google Scholar 

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We thank R. Prum for pointing out to us the literature on avian intestines, and the Harvard NSF MRSEC, the MacArthur Foundation (L.M.) and NIH RO1 HD047360 (C.J.T.) for support.

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Authors and Affiliations



C.J.T., N.A.K. and L.M. designed the research with additional contributions from T.S. and A.E.S.; T.S. (biophysical and computational experiments, data analysis), N.A.K. (biological experiments), A.E.S. (biological and biophysical experiments) and L.M. (physical mechanism, physical/mathematical model, scaling theory) did the research; P.F. (stitched physical model) and H.L. (built computational model) contributed tools; and T.S., N.A.K., L.M. and C.J.T. wrote the paper.

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Correspondence to L. Mahadevan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text and Data, Supplementary Figures 1-11 with legends, Supplementary Table 1 and additional references. (PDF 1760 kb)

Supplementary Movie 1

This movie shows gut looping simulations. Numerically computed equilibrium configurations of the gut-mesentery composite as a function of the differential growth strain between the gut and the mesentery for three representative values of the geometrical and mechanical parameters that characterize the system (see text, esp. Eq. (1)-(4) and SI for details). The top right sequence shows the length of the loops, while the bottom right sequence below shows the radius of the loops. We observe that the length of the loops does not change as a function of the differential strain (once past a threshold for the onset of the instability), but the radius decreases, as expected. (MOV 3143 kb)

Supplementary Movie 2

This movie shows the measuring of the mechanical properties of tissues. The movie on the left shows a sequence of displacements induced by a magnet on a bead that is glued to the tissue. Following calibration, this assay is used to measure the force-extension relation (shown on the right) for a piece of the mesentery, and thence its modulus. (MOV 9138 kb)

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Savin, T., Kurpios, N., Shyer, A. et al. On the growth and form of the gut. Nature 476, 57–62 (2011).

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