1. Cell Biology
  2. Developmental Biology

FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis

  1. Melissa Kelley
  2. John Yochem
  3. Michael Krieg
  4. Andrea Calixto
  5. Maxwell G Heiman
  6. Aleksandra Kuzmanov
  7. Vijaykumar Meli
  8. Martin Chalfie
  9. Miriam B Goodman
  10. Shai Shaham
  11. Alison Frand
  12. David S Fay  Is a corresponding author
  1. University of Wyoming, United States
  2. Stanford University, United States
  3. Columbia University, United States
  4. Boston Children's Hospital, United States
  5. University of California, United States
  6. Standford University, United States
  7. The Rockefeller University, United States
https://doi.org/10.7554/eLife.06565
Share this article
Cite this article
  1. Melissa Kelley
  2. John Yochem
  3. Michael Krieg
  4. Andrea Calixto
  5. Maxwell G Heiman
  6. Aleksandra Kuzmanov
  7. Vijaykumar Meli
  8. Martin Chalfie
  9. Miriam B Goodman
  10. Shai Shaham
  11. Alison Frand
  12. David S Fay
(2015)
FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis
eLife 4:e06565.
https://doi.org/10.7554/eLife.06565
  2. Download BibTeX
  3. Download .RIS

Abstract

During development, biomechanical forces contour the body and provide shape to internal organs. Using genetic and molecular approaches in combination with a FRET-based tension sensor, we characterized a pulling force exerted by the elongating pharynx (foregut) on the anterior epidermis during C. elegans embryogenesis. Resistance of the epidermis to this force and to actomyosin-based circumferential constricting forces is mediated by FBN-1, a ZP domain protein related to vertebrate fibrillins. fbn-1 was required specifically within the epidermis and FBN-1 was expressed in epidermal cells and secreted to the apical surface as a putative component of the embryonic sheath. Tiling array studies indicated that fbn-1 mRNA processing requires the conserved alternative splicing factor MEC-8/RBPMS. The conserved SYM-3/FAM102A and SYM-4/WDR44 proteins, which are linked to protein trafficking, function as additional components of this network. Our studies demonstrate the importance of the apical extracellular matrix in preventing mechanical deformation of the epidermis during development.

Article and author information

Author details

  1. Melissa Kelley

    Department of Molecular Biology, University of Wyoming, Laramie, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. John Yochem

    Department of Molecular Biology, University of Wyoming, Laramie, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Michael Krieg

    Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Andrea Calixto

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Maxwell G Heiman

    Department of Genetics, Harvard Medical School, Boston Children's Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Aleksandra Kuzmanov

    Department of Molecular Biology, University of Wyoming, Laramie, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Vijaykumar Meli

    Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Martin Chalfie

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Miriam B Goodman

    Department of Molecular and Cellular Physiology, Standford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Shai Shaham

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Alison Frand

    Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. David S Fay

    Department of Molecular Biology, University of Wyoming, Laramie, United States
    For correspondence
    davidfay@uwyo.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Julie Ahringer, University of Cambridge, United Kingdom

Version history

  1. Received: January 19, 2015
  2. Accepted: March 20, 2015
  3. Accepted Manuscript published: March 23, 2015 (version 1)
  4. Version of Record published: April 14, 2015 (version 2)

Copyright

© 2015, Kelley 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

  • 2,981
    Page views
  • 618
    Downloads
  • 40
    Citations

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

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. Melissa Kelley
  2. John Yochem
  3. Michael Krieg
  4. Andrea Calixto
  5. Maxwell G Heiman
  6. Aleksandra Kuzmanov
  7. Vijaykumar Meli
  8. Martin Chalfie
  9. Miriam B Goodman
  10. Shai Shaham
  11. Alison Frand
  12. David S Fay
(2015)
FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis
eLife 4:e06565.
https://doi.org/10.7554/eLife.06565

Share this article

https://doi.org/10.7554/eLife.06565

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression

    Heat stress impairs centromere structure and segregation of meiotic chromosomes in Arabidopsis

    Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
    Research Article

    Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.

    1. Cell Biology

    High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen

    Wan-ping Yang, Mei-qi Li ... Qian-qian Luo
    Research Article

    High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen’s ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

    1. Cell Biology

    Golgi Apparatus: Making progress

    Jurgen Denecke
    Insight

    Mapping proteins in and associated with the Golgi apparatus reveals how this cellular compartment emerges in budding yeast and progresses over time.