{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:51:25Z","timestamp":1769161885598,"version":"3.49.0"},"posted":{"date-parts":[[2024,8,13]]},"group-title":"Developmental Biology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,13]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Cell size is a key contributor to tissue morphogenesis\n                  <jats:sup>1<\/jats:sup>\n                  . As a notable example, growth plate hypertrophic chondrocytes use cellular biogenesis and disproportionate fluid uptake to expand 10-20 times in size to drive lengthening of endochondral bone\n                  <jats:sup>2,3<\/jats:sup>\n                  . Similarly, notochordal cells expand to one of the largest cell types in the developing embryo to drive axial extension\n                  <jats:sup>4\u20136<\/jats:sup>\n                  . In zebrafish, the notochord vacuolated cells undergo vacuole fusion to form a single large, fluid-filled vacuole that fills the cytoplasmic space and contributes to vacuolated cell expansion\n                  <jats:sup>7<\/jats:sup>\n                  . When this process goes awry, the notochord lacks sufficient hydrostatic pressure to support vertebral bone deposition resulting in adult spines with misshapen vertebral bones and scoliosis\n                  <jats:sup>8<\/jats:sup>\n                  . However, it remains unclear whether endochondral bone and the notochord share common genetic and cellular mechanisms for regulating cell and tissue expansion. Here, we demonstrate that the 5\u2019-inositol phosphatase gene,\n                  <jats:italic>inppl1a<\/jats:italic>\n                  , regulates notochord expansion, spine morphogenesis, and endochondral bone lengthening in zebrafish. Furthermore, we show that\n                  <jats:italic>inppl1a<\/jats:italic>\n                  regulates notochord expansion independent of vacuole fusion, thereby genetically decoupling these processes. We demonstrate that\n                  <jats:italic>inppl1a<\/jats:italic>\n                  -dependent notochord expansion is essential to establish normal mechanical properties of the notochord to facilitate the development of a straight spine. Finally, we find that\n                  <jats:italic>inppl1a<\/jats:italic>\n                  is also important for endochondral bone lengthening in fish, as has been shown in the human\n                  <jats:italic>INPPL1<\/jats:italic>\n                  -related endochondral bone disorder, Opsismodysplasia\n                  <jats:sup>9<\/jats:sup>\n                  . Overall, this work reveals a conserved mechanism of cell size regulation that influences disparate tissues critical for skeletal development and short-stature disorders.\n                <\/jats:p>","DOI":"10.1101\/2024.08.12.607640","type":"posted-content","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T05:50:18Z","timestamp":1723528218000},"source":"Crossref","is-referenced-by-count":2,"title":["A conserved regulation of cell expansion underlies notochord mechanics, spine morphogenesis, and endochondral bone lengthening"],"prefix":"10.64898","author":[{"given":"Brittney","family":"Voigt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Frazier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donya","family":"Yazdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Gontarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-5314","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane 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