{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:20:57Z","timestamp":1783621257472,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012172","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000}}],"reference-count":153,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G1001029, MR\/N021231\/1 and MR\/W001381\/1"],"award-info":[{"award-number":["G1001029, MR\/N021231\/1 and MR\/W001381\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Scoliosis affects 2\u20133% of people, often developing during and after adolescence, and currently has a lifetime chance of surgical intervention of ~0.1% in high income countries. Understanding of causal genetic and environmental factors is improving, with mechanical feedback interactions between the neuromuscular and skeletal systems thought to be important. While examining mechanosignalling in the zebrafish musculoskeletal system, we observed transient expression of\n                    <jats:italic>yap1<\/jats:italic>\n                    mRNA in precursor cells of muscle and notochord and\n                    <jats:italic>wwtr1<\/jats:italic>\n                    mRNA accumulation in differentiated muscle. Yap1 and Wwtr1\/Taz are transcriptional coactivators that mediate Hippo pathway signalling, often in response to mechanosignals. Loss of function mutation of either gene alone transiently altered early larval motility and reduced survival to adulthood, but mutation of\n                    <jats:italic>yap1<\/jats:italic>\n                    specifically diminished overall growth without an obvious histological muscle defect.\n                    <jats:italic>Yap1<\/jats:italic>\n                    mutants had a temperature-sensitive phenotype of oedema in cardiac and other tissues, which could be rescued by rearing at low temperature. Rescued\n                    <jats:italic>yap1<\/jats:italic>\n                    mutants showed focal defects in hypochordal\n                    <jats:italic>col8a1a<\/jats:italic>\n                    mRNA expression at 1\u20132 days post-fertilisation (dpf), an early motility defect at 5 dpf and subsequently developed a fully penetrant vertebral dysmorphology, reflected by a decrease in posterior vertebral height. Thereafter, frank kyphoscoliosis accompanied by additional vertebral defects developed in around a third of the surviving\n                    <jats:italic>yap1<\/jats:italic>\n                    mutants and was first detected at 11 dpf. Thus, the mild initial vertebral defect can, in a predisposing genetic or environmental background, gradually develop into full kyphoscoliosis through a positive feedback mechanism, analogous to the Hueter-Volkmann \u2018Law\u2019. Although the cell type\/s of cell autonomous\n                    <jats:italic>yap1<\/jats:italic>\n                    action remain unclear, we hypothesise that Yap1 mechanosensation mediates feedback between bone, muscle and tendon to restrain vertebral overgrowth and protect against the development of kyphoscoliosis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012172","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T17:39:37Z","timestamp":1779989977000},"page":"e1012172","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Yap1 regulates motility and vertebral development and prevents kyphoscoliosis in zebrafish"],"prefix":"10.1371","volume":"22","author":[{"given":"Victoria C.","family":"Williams-Ward","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-9853","authenticated-orcid":true,"given":"Kees","family":"Wanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-9225","authenticated-orcid":true,"given":"Simon M.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"pgen.1012172.ref001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41413-020-0089-0","article-title":"The cartilage matrisome in adolescent idiopathic scoliosis","volume":"8","author":"CA Wise","year":"2020","journal-title":"Bone 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