Article | Published:

On the growth and form of the gut

Nature volume 476, pages 5762 (04 August 2011) | Download Citation

Abstract

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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Acknowledgements

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.

Author information

Author notes

    • Thierry Savin
    • , Natasza A. Kurpios
    •  & Haiyi Liang

    Present addresses: Department of Materials, Polymer Physics, ETH Zürich, 8093 Zürich, Switzerland (T.S.); Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA (N.A.K.); Department of Modern Mechanics, USTC-Hefei, Anhui 230027, China (H.L.).

    • Thierry Savin
    • , Natasza A. Kurpios
    •  & Amy E. Shyer

    These authors contributed equally to this work.

Affiliations

  1. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

    • Thierry Savin
    • , Patricia Florescu
    • , Haiyi Liang
    •  & L. Mahadevan
  2. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Natasza A. Kurpios
    • , Amy E. Shyer
    •  & Clifford J. Tabin
  3. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • L. Mahadevan
  4. Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA

    • L. Mahadevan
  5. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA

    • L. Mahadevan
  6. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA

    • L. Mahadevan
  7. Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, Massachusetts 02138, USA

    • L. Mahadevan

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to L. Mahadevan.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Text and Data, Supplementary Figures 1-11 with legends, Supplementary Table 1 and additional references.

Videos

  1. 1.

    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.

  2. 2.

    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.

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DOI

https://doi.org/10.1038/nature10277

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