{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:40:50Z","timestamp":1790383250617,"version":"4.1.0"},"reference-count":53,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Novo Nordisk","award":["NNF21CC0073729"],"award-info":[{"award-number":["NNF21CC0073729"]}]},{"name":"ZonMw","award":["10250022120002"],"award-info":[{"award-number":["10250022120002"]}]},{"name":"ZonMw","award":["40-46800-98-015"],"award-info":[{"award-number":["40-46800-98-015"]}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"crossref","award":["VI.Vidi.203.050"],"award-info":[{"award-number":["VI.Vidi.203.050"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Universiteit Leiden"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Axial elongation and cell fate decisions during early embryonic development are regulated by gradients of signaling molecules, such as retinoic acid (RA) and fibroblast growth factor (FGF). To assess the role of RA in vitro, studies have relied on its direct addition to the medium, which can produce teratogenic effects. Here, we examined the role of a RA precursor, retinol, on axial elongation, anteroposterior development, and FGF-dependent signaling in murine gastruloids, an in vitro model system for early embryogenesis. Rather than applying RA ectopically, we supplemented a retinoid-free medium with its precursor, retinol, prompting the cells to produce RA endogenously. Our results showed that the spatiotemporal RA and FGF signaling can be manipulated with different doses of retinol, influencing gastruloid elongation and lineage specification. Gastruloids cultured in high doses of retinol showed an enrichment of ectoderm, whereas low doses resulted in early mesoderm specification and increased FGF signaling. We further used our approach to confirm that RA signaling inhibits FGF in gastruloids. Thus, retinol can modulate cellular composition in gastruloids, allowing us to investigate fate commitment of ectoderm and mesoderm progenitors in vitro.<\/jats:p>","DOI":"10.1242\/dev.205153","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:25:41Z","timestamp":1783409141000},"source":"Crossref","is-referenced-by-count":1,"title":["Retinoic acid and FGF signaling interact to control elongation and lineage specification in a mouse gastruloid model"],"prefix":"10.1242","volume":"153","author":[{"given":"Mehmet","family":"Yildiz","sequence":"first","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-0899","authenticated-orcid":false,"given":"No\u00eblle","family":"Dommann","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugce Kardelen","family":"Hasdemir","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"de Vries","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Alemany","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale F.","family":"Dijkers","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3592-4353","authenticated-orcid":false,"given":"Niels","family":"Geijsen","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 Department of Anatomy and Embryology , , 2300RC Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2300RC Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026090107113617600_DEV205153C1","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1101\/gad.855001","article-title":"The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures","volume":"15","author":"Abu-Abed","year":"2001","journal-title":"Genes Dev."},{"key":"2026090107113617600_DEV205153C2","doi-asserted-by":"publisher","first-page":"6501","DOI":"10.1016\/j.bmcl.2008.10.054","article-title":"The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901","volume":"18","author":"Barrett","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090107113617600_DEV205153C3","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41586-018-0578-0","article-title":"Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids","volume":"562","author":"Beccari","year":"2018","journal-title":"Nature"},{"key":"2026090107113617600_DEV205153C4","doi-asserted-by":"publisher","first-page":"20190556","DOI":"10.1098\/rstb.2019.0556","article-title":"Mesoderm patterning by a dynamic gradient of retinoic acid signalling","volume":"375","author":"Bernheim","year":"2020","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. 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