Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology
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 o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/83883 |
| _version_ | 1797954851534012416 |
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| author | Elizabeth A Bearce Zoe H Irons Johnathan R O'Hara-Smith Colin J Kuhns Sophie I Fisher William E Crow Daniel T Grimes |
| author_facet | Elizabeth A Bearce Zoe H Irons Johnathan R O'Hara-Smith Colin J Kuhns Sophie I Fisher William E Crow Daniel T Grimes |
| author_sort | Elizabeth A Bearce |
| collection | DOAJ |
| description | 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 these 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 in 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. |
| first_indexed | 2024-04-10T23:25:08Z |
| format | Article |
| id | doaj.art-43f7a1eac97d4b55a49013a64399c982 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T23:25:08Z |
| publishDate | 2022-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-43f7a1eac97d4b55a49013a64399c9822023-01-12T12:35:38ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.83883Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphologyElizabeth A Bearce0Zoe H Irons1Johnathan R O'Hara-Smith2Colin J Kuhns3Sophie I Fisher4William E Crow5https://orcid.org/0000-0003-2991-3076Daniel T Grimes6https://orcid.org/0000-0003-0173-1887Institute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesInstitute of Molecular Biology, Department of Biology, University of Oregon, Eugene, United StatesThe 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 these 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 in 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.https://elifesciences.org/articles/83883zebrafishurotensin II-related peptidescoliosislordosisciliareissner fiber |
| spellingShingle | Elizabeth A Bearce Zoe H Irons Johnathan R O'Hara-Smith Colin J Kuhns Sophie I Fisher William E Crow Daniel T Grimes Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology eLife zebrafish urotensin II-related peptide scoliosis lordosis cilia reissner fiber |
| title | Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology |
| title_full | Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology |
| title_fullStr | Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology |
| title_full_unstemmed | Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology |
| title_short | Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology |
| title_sort | urotensin ii related peptides urp1 and urp2 control zebrafish spine morphology |
| topic | zebrafish urotensin II-related peptide scoliosis lordosis cilia reissner fiber |
| url | https://elifesciences.org/articles/83883 |
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