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.

Urp1 and Urp2 act redundantly to maintain spine shape in zebrafish larvae

“…This suggests that Urp1/2-Uts2r3 signaling is actually dispensable for embryogenesis. Consistent with this idea, we have previously reported that, in Xenopus, CRISPR-mediated inhibition of utr4 (the counterpart of zebrafish uts2r3) does not provoke axis curvature defect in embryos but results in curled-down phenotype in tadpoles, similar to that observed in zebrafish uts2r3 mutant larvae (Alejevski et al, 2021). This suggests that the mechanisms involved in body axis morphogenesis are conserved between fishes and amphibians.…”

“…In Xenopus laevis (African clawed frogs), we found that urp2 is produced by the CSF-cNs, while utr4 , the Xenopus counterpart of uts2r3, is expressed in dorsal somites during embryogenesis. Furthermore, CRISPR-based inhibition of utr4 induces an axis defect in Xenopus tadpoles, similar to that of zebrafish uts2r3 mutant larvae (Alejevski et al, 2021). This suggests that the function of Urp1/2 signaling in body axis is conserved in at least some tetrapods.…”

“…These cells secrete the neuropeptides Urp1/2 that act through Uts2r3 on dorsal somitic muscles to promote axis straightening, possibly through the regulation of muscle tone. Of note, we recently reported that urp2 exists in clawed frogs (Alejevski et al, 2021). In Xenopus laevis (African clawed frogs), we found that urp2 is produced by the CSF-cNs, while utr4 , the Xenopus counterpart of uts2r3, is expressed in dorsal somites during embryogenesis.…”

“…Characterized first in the Japanese eel ( Anguilla) (Nobata et al, 2011) and in the zebrafish (Parmentier et al, 2011), urp1 and urp2 seem to exist in all fishes but to have been lost in mammals. However, urp2 has recently also been identified in Xenopus (clawed frogs) (Alejevski et al, 2021). All peptides of the Uts2 family have been suggested to act through a multigenic family of G protein-coupled receptors called Uts2r (also known as Utr or UT).…”

Turning the Curve Into Straight: Phenogenetics of the Spine Morphology and Coordinate Maintenance in the Zebrafish

“…While developmental and morphological differences exist between spines from distinct vertebrate species, a common evolutionary origin has been proposed for this skeletal structure. Indeed, the straight morphology of the VC is conferred by conserved molecules and signaling pathways orchestrating the establishment and maintenance of the spine 3D axial plane ( Brand-Saberi and Christ, 2000 ; Alejevski et al, 2021 ). However, our understanding of the identity and function of the molecules regulating spine morphology remains elusive because of the lack of tools to develop genetically tractable models to link genomic sequences with AIS.…”