1. Cell Biology
  2. Developmental Biology
Download icon

Radially-patterned cell behaviours during tube budding from an epithelium

  1. Yara E Sanchez-Corrales
  2. Guy B Blanchard  Is a corresponding author
  3. Katja Röper  Is a corresponding author
  1. University of Cambridge, United Kingdom
Research Article
  • Cited 19
  • Views 3,168
  • Annotations
Cite this article as: eLife 2018;7:e35717 doi: 10.7554/eLife.35717

Abstract

The budding of tubular organs from flat epithelial sheets is a vital morphogenetic process. Cell behaviours that drive such processes are only starting to be unraveled. Using live-imaging and novel morphometric methods we show that in addition to apical constriction, radially-oriented directional intercalation of cells plays a major contribution to early stages of invagination of the salivary gland tube in the Drosophila embryo. Extending analyses in 3D, we find that near the pit of invagination, isotropic apical constriction leads to strong cell-wedging. Further from the pit cells interleave circumferentially, suggesting apically-driven behaviours. Supporting this, junctional myosin is enriched in, and neighbour exchanges are biased towards the circumferential orientation. In a mutant failing pit specification, neither are biased due to an inactive pit. Thus, tube budding involves radially-patterned pools of apical myosin, medial as well as junctional, and radially-patterned 3D-cell behaviours, with a close mechanical interplay between invagination and intercalation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures.

Article and author information

Author details

  1. Yara E Sanchez-Corrales

    MRC-Laboratory of Molecular Biology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1438-1994
  2. Guy B Blanchard

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    gb288@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  3. Katja Röper

    MRC -Laboratory of Molecular Biology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    kroeper@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3361-766X

Funding

Medical Research Council (U105178780)

  • Yara E Sanchez-Corrales
  • Guy B Blanchard
  • Katja Röper

Biotechnology and Biological Sciences Research Council (BB/J010278/1)

  • Guy B Blanchard

Wellcome (100329/Z/12/Z)

  • Guy B Blanchard

Isaac Newton Trust (15.23(k))

  • Guy B Blanchard

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

Reviewing Editor

  1. Stefan Luschnig

Publication history

  1. Received: February 6, 2018
  2. Accepted: July 16, 2018
  3. Accepted Manuscript published: July 17, 2018 (version 1)
  4. Accepted Manuscript updated: July 23, 2018 (version 2)
  5. Accepted Manuscript updated: July 24, 2018 (version 3)
  6. Version of Record published: August 13, 2018 (version 4)

Copyright

© 2018, Sanchez-Corrales 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

  • 3,168
    Page views
  • 413
    Downloads
  • 19
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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)

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

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

Further reading

    1. Cell Biology
    2. Neuroscience
    Vladimir Zhemkov et al.
    Research Article

    Sigma 1 receptor (S1R) is a 223-amino-acid-long transmembrane endoplasmic reticulum (ER) protein. S1R modulates activity of multiple effector proteins and is a well-established drug target. However, signaling functions of S1R in cells are poorly understood. Here, we test the hypothesis that biological activity of S1R in cells can be explained by its ability to interact with cholesterol and to form cholesterol-enriched microdomains in the ER membrane. By performing experiments in reduced reconstitution systems, we demonstrate direct effects of cholesterol on S1R clustering. We identify a novel cholesterol-binding motif in the transmembrane region of human S1R. Mutations of this motif impair association of recombinant S1R with cholesterol beads, affect S1R clustering in vitro and disrupt S1R subcellular localization. We demonstrate that S1R-induced membrane microdomains have increased local membrane thickness and that increased local cholesterol concentration and/or membrane thickness in these microdomains can modulate signaling of inositol-requiring enzyme 1α in the ER. Further, S1R agonists cause disruption of S1R clusters, suggesting that biological activity of S1R agonists is linked to remodeling of ER membrane microdomains. Our results provide novel insights into S1R-mediated signaling mechanisms in cells.

    1. Cell Biology
    2. Developmental Biology
    Yuki Osawa et al.
    Research Article

    The male germ cells must adopt the correct morphology at each differentiation stage for proper spermatogenesis. The spermatogonia regulates its differentiation state by its own migration. The male germ cells differentiate and mature with the formation of syncytia, failure of forming the appropriate syncytia results in the arrest at the spermatocyte stage. However, the detailed molecular mechanisms of male germ cell morphological regulation are unknown. Here, we found that EXOC1, a member of the Exocyst complex, is important for the pseudopod formation of spermatogonia and spermatocyte syncytia in mice. EXOC1 contributes to the pseudopod formation of spermatogonia by inactivating the Rho family small GTPase Rac1 and also functions in the spermatocyte syncytia with the SNARE proteins STX2 and SNAP23. Since EXOC1 is known to bind to several cell morphogenesis factors, this study is expected to be the starting point for the discovery of many morphological regulators of male germ cells.