Notochord vacuoles absorb compressive bone growth during zebrafish spine formation
- Duke University, United States
- University of California, San Francisco, United States
- Boston College, United States
- Max Planck Institute for Heart and Lung Research, Germany
Abstract
The vertebral column or spine assembles around the notochord rod which contains a core made of large vacuolated cells. Each vacuolated cell possesses a single fluid-filled vacuole, and loss or fragmentation of these vacuoles in zebrafish leads to spine kinking. Here, we identified a mutation in the kinase gene dstyk that causes fragmentation of notochord vacuoles and a severe congenital scoliosis-like phenotype in zebrafish. Live imaging revealed that Dstyk regulates fusion of membranes with the vacuole. We find that localized disruption of notochord vacuoles causes vertebral malformation and curving of the spine axis at those sites. Accordingly, in dstyk mutants the spine curves increasingly over time as vertebral bone formation compresses the notochord asymmetrically, causing vertebral malformations and kinking of the axis. Together, our data show that notochord vacuoles function as a hydrostatic scaffold that guides symmetrical growth of vertebrae and spine formation.
Data availability
All data generated or analyses during this study are included in the manuscript and supporting files. Source data files have been provided as indicated. Data has been deposited to Dryad, under the DOI: 10.5061/dryad.73n5tb2tb. Due to their large size, raw image files can be accessed upon request.
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Data from: Notochord vacuoles absorb compressive bone growth during zebrafish spine formationDryad Digital Repository, doi:10.5061/dryad.73n5tb2tb.
Article and author information
Author details
Didier YR Stainier
Funding
National Institutes of Health (R01AR065439)
- Michel Bagnat
Howard Hughes Medical Institute (Faculty Scholars)
- Michel Bagnat
National Institutes of Health (R01HL54737)
- Didier YR Stainier
National Institutes of Health (R00GM105874 and R03HD091634)
- Sarah K McMenamin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Lilianna Solnica-Krezel, Washington University School of Medicine, United States
Ethics
Animal experimentation: Zebrafish (Danio rerio) were used in accordance with Duke University Institutional Animal Care and Use Committee (IACUC) guidelines and approved under our animal protocol A089-17-04
Version history
- Received: August 20, 2019
- Accepted: January 28, 2020
- Accepted Manuscript published: January 29, 2020 (version 1)
- Version of Record published: February 11, 2020 (version 2)
Copyright
© 2020, Bagwell 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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Notochord vacuoles absorb compressive bone growth during zebrafish spine formation
eLife 9:e51221.
https://doi.org/10.7554/eLife.51221
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