The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium
- University of Toronto, Canada
Abstract
In emerging epithelial tissues, cells undergo dramatic rearrangements to promote tissue shape changes. Dividing cells remain interconnected via transient cytokinetic bridges. Bridges are cleaved during abscission and currently, the consequences of disrupting abscission in developing epithelia are not well understood. We show that the Rab GTPase, Rab25, localizes near cytokinetic midbodies and likely coordinates abscission through endomembrane trafficking in the epithelium of the zebrafish gastrula during epiboly. In maternal-zygotic Rab25a and Rab25b mutant embryos, morphogenic activity tears open persistent apical cytokinetic bridges that failed to undergo timely abscission. Cytokinesis defects result in anisotropic cell morphologies that are associated with a reduction of contractile actomyosin networks. This slows cell rearrangements and alters the viscoelastic responses of the tissue, all of which likely contribute to delayed epiboly. We present a model in which Rab25 trafficking coordinates cytokinetic bridge abscission and cortical actin density, impacting local cell shape changes and tissue-scale forces.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Rodrigo Fernandez-Gonzalez
Funding
Natural Sciences and Engineering Research Council of Canada (RGPIN-2018-04862)
- Ashley E E Bruce
Canadian Institutes of Health Research (156279)
- Rodrigo Fernandez-Gonzalez
Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-05972)
- Jennifer A Mitchell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Michel Bagnat, Duke University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Canadian Council on Animal Care Guidelines on the Care and Use of Fish in Research. All the animals were handled and maintained according to a protocol (Protocol Number: 20012462) approved by the Biological Sciences Local Animal Care Committee at the University of Toronto.
Version history
- Received: December 23, 2020
- Accepted: March 22, 2021
- Accepted Manuscript published: March 23, 2021 (version 1)
- Version of Record published: April 9, 2021 (version 2)
- Version of Record updated: May 19, 2022 (version 3)
Copyright
© 2021, Willoughby 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.
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The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium
eLife 10:e66060.
https://doi.org/10.7554/eLife.66060
Further reading
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- Cell Biology
- Neuroscience
Mutations in Drosophila Swiss Cheese (SWS) gene or its vertebrate orthologue Neuropathy Target Esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well-established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain-barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.
