Cell volume changes contribute to epithelial morphogenesis in zebrafish Kupffer's vesicle

  1. Agnik Dasgupta
  2. Matthias Merkel
  3. Madeline J Clark
  4. Andrew E Jacob
  5. Jonathan Edward Dawson
  6. M Lisa Manning  Is a corresponding author
  7. Jeffrey D Amack  Is a corresponding author
  1. State University of New York, Upstate Medical University, United States
  2. Syracuse University, United States

Abstract

How epithelial cell behaviors are coordinately regulated to sculpt tissue architecture is a fundamental question in biology. Kupffer's vesicle (KV), a transient organ with a fluid-filled lumen, provides a simple system to investigate the interplay between intrinsic cellular mechanisms and external forces during epithelial morphogenesis. Using 3-dimensional (3D) analyses of single cells we identify asymmetric cell volume changes along the anteroposterior axis of KV that coincide with asymmetric cell shape changes. Blocking ion flux prevents these cell volume changes and cell shape changes. Vertex simulations suggest cell shape changes do not depend on lumen expansion. Consistent with this prediction, asymmetric changes in KV cell volume and shape occur normally when KV lumen growth fails due to leaky cell adhesions. These results indicate ion flux mediates cell volume changes that contribute to asymmetric cell shape changes in KV, and that these changes in epithelial morphology are separable from lumen-generated forces.

Article and author information

Author details

  1. Agnik Dasgupta

    Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0860-1006
  2. Matthias Merkel

    Department of Physics, Syracuse University, Syracuse, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9118-1270
  3. Madeline J Clark

    Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Andrew E Jacob

    Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jonathan Edward Dawson

    Department of Physics, Syracuse University, Syracuse, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9770-8475
  6. M Lisa Manning

    Department of Physics, Syracuse University, Syracuse, United States
    For correspondence
    mmanning@syr.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Jeffrey D Amack

    Department of Cell and Developmental Bilogy, State University of New York, Upstate Medical University, Syracuse, United States
    For correspondence
    amackj@upstate.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5465-9754

Funding

National Institutes of Health (R01HL095690)

  • Jeffrey D Amack

National Institutes of Health (R01GM117598)

  • M Lisa Manning

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

Copyright

© 2018, Dasgupta 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

  • 3,858
    views
  • 477
    downloads
  • 35
    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. Agnik Dasgupta
  2. Matthias Merkel
  3. Madeline J Clark
  4. Andrew E Jacob
  5. Jonathan Edward Dawson
  6. M Lisa Manning
  7. Jeffrey D Amack
(2018)
Cell volume changes contribute to epithelial morphogenesis in zebrafish Kupffer's vesicle
eLife 7:e30963.
https://doi.org/10.7554/eLife.30963

Share this article

https://doi.org/10.7554/eLife.30963

Further reading

    1. Cell Biology
    Kaili Du, Hongyu Chen ... Dan Li
    Research Article

    Niemann–Pick disease type C (NPC) is a devastating lysosomal storage disease characterized by abnormal cholesterol accumulation in lysosomes. Currently, there is no treatment for NPC. Transcription factor EB (TFEB), a member of the microphthalmia transcription factors (MiTF), has emerged as a master regulator of lysosomal function and promoted the clearance of substrates stored in cells. However, it is not known whether TFEB plays a role in cholesterol clearance in NPC disease. Here, we show that transgenic overexpression of TFEB, but not TFE3 (another member of MiTF family) facilitates cholesterol clearance in various NPC1 cell models. Pharmacological activation of TFEB by sulforaphane (SFN), a previously identified natural small-molecule TFEB agonist by us, can dramatically ameliorate cholesterol accumulation in human and mouse NPC1 cell models. In NPC1 cells, SFN induces TFEB nuclear translocation via a ROS-Ca2+-calcineurin-dependent but MTOR-independent pathway and upregulates the expression of TFEB-downstream genes, promoting lysosomal exocytosis and biogenesis. While genetic inhibition of TFEB abolishes the cholesterol clearance and exocytosis effect by SFN. In the NPC1 mouse model, SFN dephosphorylates/activates TFEB in the brain and exhibits potent efficacy of rescuing the loss of Purkinje cells and body weight. Hence, pharmacological upregulating lysosome machinery via targeting TFEB represents a promising approach to treat NPC and related lysosomal storage diseases, and provides the possibility of TFEB agonists, that is, SFN as potential NPC therapeutic candidates.

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.