Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology
- University of Oregon, United States
Abstract
The spine provides structure and support to the body, yet how it develops its characteristic morphology as the organism grows is little understood. This is underscored by the commonality of conditions in which the spine curves abnormally such as scoliosis, kyphosis and lordosis. Understanding the origin of such spinal curves has been challenging in part due to the lack of appropriate animal models. Recently, zebrafish have emerged as promising tools with which to understand the origin of spinal curves. Using zebrafish, we demonstrate that the Urotensin II-related peptides (URPs), Urp1 and Urp2, are essential for maintaining spine morphology. Urp1 and Urp2 are 10-amino acid cyclic peptides expressed by neurons lining the central canal of the spinal cord. Upon combined genetic loss of Urp1 and Urp2, adolescent-onset planar curves manifested in the caudal region of the spine. Highly similar curves were caused by mutation of Uts2r3, an URP receptor. Quantitative comparisons revealed that Urotensin-associated curves were distinct from other zebrafish spinal curve mutants in curve position and direction. Last, we found that the Reissner fiber, a proteinaceous thread that sits in the central canal and has been implicated in the control of spine morphology, breaks down prior to curve formation mutants with perturbed cilia motility but was unaffected by loss of Uts2r3. This suggests a Reissner fiber-independent mechanism of curvature in Urotensin-deficient mutants. Overall, our results show that Urp1 and Urp2 control zebrafish spine morphology and establish new animal models of spine deformity.
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All data generated or analysed during this study are included in the manuscript and supporting file.
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Funding
National Institutes of Health (R00AR70905)
- Daniel T Grimes
National Institutes of Health (F32AR078002)
- Elizabeth A Bearce
National Institutes of Health (F31HD105435)
- Zoe H Irons
National Institutes of Health (R35GM142949)
- Daniel T Grimes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were undertaken in accordance with research guidelines of the International Association for Assessment and Accreditation of Laboratory Animal Care and approved by the University of Oregon Institutional Animal Care and Use Committee (# AUP-21-45).
Copyright
© 2022, Bearce 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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Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology
eLife 11:e83883.
https://doi.org/10.7554/eLife.83883
