Visceral organ morphogenesis via calcium-patterned muscle constrictions

  1. Noah P Mitchell
  2. Dillon J Cislo
  3. Suraj Shankar
  4. Yuzheng Lin
  5. Boris I Shraiman
  6. Sebastian J Streichan  Is a corresponding author
  1. University of California, Santa Barbara, United States

Abstract

Organ architecture is often composed of multiple laminar tissues arranged in concentric layers. During morphogenesis, the initial geometry of visceral organs undergoes a sequence of folding, adopting a complex shape that is vital for function. Genetic signals are known to impact form, yet the dynamic and mechanical interplay of tissue layers giving rise to organs' complex shapes remains elusive. Here, we trace the dynamics and mechanical interactions of a developing visceral organ across tissue layers, from sub-cellular to organ scale in vivo. Combining deep tissue light-sheet microscopy for in toto live visualization with a novel computational framework for multilayer analysis of evolving complex shapes, we find a dynamic mechanism for organ folding using the embryonic midgut of Drosophila as a model visceral organ. Hox genes, known regulators of organ shape, control the emergence of high-frequency calcium pulses. Spatiotemporally patterned calciumpulses triggermuscle contractions via myosin light chain kinase. Muscle contractions, in turn, induce cell shape change in the adjacent tissue layer. This cell shape change collectively drives a convergent extension pattern. Through tissue incompressibility and initial organ geometry, this in-plane shape change is linked to out-of-plane organ folding. Our analysis follows tissue dynamics during organ shape change in vivo, tracing organ-scale folding to a high-frequency molecular mechanism. These findings offer a mechanical route for gene expression to induce organ shape change: genetic patterning in one layer triggers a physical process in the adjacent layer - revealing post-translational mechanisms that govern shape change.

Data availability

We have uploaded processed data for experiments spanning all figures to FigShare, available at https://figshare.com/authors/Noah_Mitchell/12456507 in project #137793: 'Visceral organ morphogenesis via calcium-patterned constrictions'. The original volumetric data from living imaging are each up to a terabyte in size. We therefore posted processed data on FigShare, including 2D pullback image sequences of the dynamic 3D tissue surfaces, volumetric data for small datasets, and processed tables. An interested researcher would be able to access the original data on our lab server. They would need to contact Sebastian Streichan (streicha@ucsb.edu) to be added to the server's list of users and could then download the original data directly.In addition to the TubULAR package detailed in reference 32, further software and scripts used to analyze the data is available at: https://github.com/npmitchell/VisceralOrganMorphogenesisViaCalciumPatternedMuscleConstrictions.

The following data sets were generated

Article and author information

Author details

  1. Noah P Mitchell

    Kavli Institute for Theoretical Physics, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dillon J Cislo

    Department of Physics, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Suraj Shankar

    Kavli Institute for Theoretical Physics, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4615-975X
  4. Yuzheng Lin

    Department of Physics, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Boris I Shraiman

    Kavli Institute for Theoretical Physics, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0886-8990
  6. Sebastian J Streichan

    Department of Physics, University of California, Santa Barbara, Santa Barbara, United States
    For correspondence
    streicha@ucsb.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6105-9087

Funding

National Institutes of Health (R35 GM138203)

  • Sebastian J Streichan

National Institutes of Health (R00 294 HD088708)

  • Sebastian J Streichan

Helen Hay Whitney Foundation (F-1246)

  • Noah P Mitchell

National Science Foundation (PHY-1748958)

  • Boris I Shraiman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Mitchell et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,267
    views
  • 723
    downloads
  • 29
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Noah P Mitchell
  2. Dillon J Cislo
  3. Suraj Shankar
  4. Yuzheng Lin
  5. Boris I Shraiman
  6. Sebastian J Streichan
(2022)
Visceral organ morphogenesis via calcium-patterned muscle constrictions
eLife 11:e77355.
https://doi.org/10.7554/eLife.77355

Share this article

https://doi.org/10.7554/eLife.77355

Further reading

    1. Developmental Biology
    Satoshi Yamashita, Shuji Ishihara, François Graner
    Research Article

    Apical constriction is a basic mechanism for epithelial morphogenesis, making columnar cells into wedge shape and bending a flat cell sheet. It has long been thought that an apically localized myosin generates a contractile force and drives the cell deformation. However, when we tested the increased apical surface contractility in a cellular Potts model simulation, the constriction increased pressure inside the cell and pushed its lateral surface outward, making the cells adopt a drop shape instead of the expected wedge shape. To keep the lateral surface straight, we considered an alternative model in which the cell shape was determined by cell membrane elasticity and endocytosis, and the increased pressure is balanced among the cells. The cellular Potts model simulation succeeded in reproducing the apical constriction, and it also suggested that a too strong apical surface tension might prevent the tissue invagination.

    1. Cancer Biology
    2. Developmental Biology
    Sara Jaber, Eliana Eldawra ... Franck Toledo
    Research Article

    Missense ‘hotspot’ mutations localized in six p53 codons account for 20% of TP53 mutations in human cancers. Hotspot p53 mutants have lost the tumor suppressive functions of the wildtype protein, but whether and how they may gain additional functions promoting tumorigenesis remain controversial. Here, we generated Trp53Y217C, a mouse model of the human hotspot mutant TP53Y220C. DNA damage responses were lost in Trp53Y217C/Y217C (Trp53YC/YC) cells, and Trp53YC/YC fibroblasts exhibited increased chromosome instability compared to Trp53-/- cells. Furthermore, Trp53YC/YC male mice died earlier than Trp53-/- males, with more aggressive thymic lymphomas. This correlated with an increased expression of inflammation-related genes in Trp53YC/YC thymic cells compared to Trp53-/- cells. Surprisingly, we recovered only one Trp53YC/YC female for 22 Trp53YC/YC males at weaning, a skewed distribution explained by a high frequency of Trp53YC/YC female embryos with exencephaly and the death of most Trp53YC/YC female neonates. Strikingly, however, when we treated pregnant females with the anti-inflammatory drug supformin (LCC-12), we observed a fivefold increase in the proportion of viable Trp53YC/YC weaned females in their progeny. Together, these data suggest that the p53Y217C mutation not only abrogates wildtype p53 functions but also promotes inflammation, with oncogenic effects in males and teratogenic effects in females.