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Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod.

ABSTRACT: Urp1 and Urp2 are two neuropeptides of the urotensin II family identified in teleost fish and mainly expressed in cerebrospinal fluid (CSF)-contacting neurons. It has been recently proposed that Urp1 and Urp2 are required for correct axis formation and maintenance. Their action is thought to be mediated by the receptor Uts2r3, which is specifically expressed in dorsal somites. In support of this view, it has been demonstrated that the loss of uts2r3 results in severe scoliosis in adult zebrafish. In the present study, we report for the first time the occurrence of urp2, but not of urp1, in two tetrapod species of the Xenopus genus. In X. laevis, we show that urp2 mRNA-containing cells are CSF-contacting neurons. Furthermore, we identified utr4, the X. laevis counterparts of zebrafish uts2r3, and we demonstrate that, as in zebrafish, it is expressed in the dorsal somatic musculature. Finally, we reveal that, in X. laevis, the disruption of utr4 results in an abnormal curvature of the antero-posterior axis of the tadpoles. Taken together, our results suggest that the role of the Utr4 signalling pathway in the control of body straightness is an ancestral feature of bony vertebrates and not just a peculiarity of ray-finned fishes.

SUBMITTER: Alejevski F

PROVIDER: S-EPMC8354755 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod.

Alejevski Faredin F Leemans Michelle M Gaillard Anne-Laure AL Leistenschneider David D de Flori Céline C Bougerol Marion M Le Mével Sébastien S Herrel Anthony A Fini Jean-Baptiste JB Pézeron Guillaume G Tostivint Hervé H

Open biology 20210811 8

Urp1 and Urp2 are two neuropeptides of the urotensin II family identified in teleost fish and mainly expressed in cerebrospinal fluid (CSF)-contacting neurons. It has been recently proposed that Urp1 and Urp2 are required for correct axis formation and maintenance. Their action is thought to be mediated by the receptor Uts2r3, which is specifically expressed in dorsal somites. In support of this view, it has been demonstrated that the loss of <i>uts2r3</i> results in severe scoliosis in adult ze ...[more]

PMID: 34375549

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Project description:Urotensin-II is a polypeptide ligand with neurohormone-like activity. It mediates downstream signaling pathways through G-protein-coupled receptor 14 (GPR14) also known as urotensin receptor (UTR). Urotensin-II is the most potent endogenous vasoconstrictor in mammals, promoting cardiovascular remodelling, cardiac fibrosis, and cardiomyocyte hypertrophy. It is also involved in other physiological and pathological activities, including neurosecretory effects, insulin resistance, atherosclerosis, kidney disease, and carcinogenic effects. Moreover, it is a notable player in the process of inflammatory injury, which leads to the development of inflammatory diseases. Urotensin-II/UTR expression stimulates the accumulation of monocytes and macrophages, which promote the adhesion molecules expression, chemokines activation and release of inflammatory cytokines at inflammatory injury sites. Therefore, urotensin-II turns out to be an important therapeutic target for the treatment options and management of associated diseases. The main downstream signaling pathways mediated through this urotensin-II /UTR system are RhoA/ROCK, MAPKs and PI3K/AKT. Due to the importance of urotensin-II systems in biomedicine, we consolidated a network map of urotensin-II /UTR signaling. The described signaling map comprises 33 activation/inhibition events, 31 catalysis events, 15 molecular associations, 40 gene regulation events, 60 types of protein expression, and 11 protein translocation events. The urotensin-II signaling pathway map is made freely accessible through the WikiPathways Database ( https://www.wikipathways.org/index.php/Pathway:WP5158 ). The availability of comprehensive urotensin-II signaling in the public resource will help understand the regulation and function of this pathway in normal and pathological conditions. We believe this resource will provide a platform to the scientific community in facilitating the identification of novel therapeutic drug targets for diseases associated with urotensin-II signaling.

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Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod.

Publications

Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod.

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