{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:27:31Z","timestamp":1791275251108,"version":"4.1.0"},"reference-count":74,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["20H03264"],"award-info":[{"award-number":["20H03264"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"award":["20H03264"],"award-info":[{"award-number":["20H03264"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["24K02034"],"award-info":[{"award-number":["24K02034"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"award":["24K02034"],"award-info":[{"award-number":["24K02034"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["24KJ1718"],"award-info":[{"award-number":["24KJ1718"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"award":["24KJ1718"],"award-info":[{"award-number":["24KJ1718"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Axolotls (\n                    <jats:italic>Ambystoma mexicanum<\/jats:italic>\n                    ) exhibit a remarkable ability to regenerate limbs. Classical experiments have suggested that contact between cells derived from distinct orientations\u2014dorsal, ventral, anterior, and posterior\u2014within the regenerating blastema is necessary for accurate limb pattern formation. However, the molecular basis for this requirement has remained largely unknown. Here, we demonstrate that both dorsal and ventral tissues are required for limb formation via induction of\n                    <jats:italic>Shh<\/jats:italic>\n                    expression, which plays a crucial role in limb patterning. Using the accessory limb model, we induced position-specific blastemas lacking cells derived from a single orientation (anterior, posterior, dorsal, or ventral). Limb patterning occurred only in blastemas containing both dorsal- and ventral-derived cells. We further observed that\n                    <jats:italic>Shh<\/jats:italic>\n                    expression requires dorsoventral contact within a blastema, highlighting the necessity of dorsoventral contact for inducing\n                    <jats:italic>Shh<\/jats:italic>\n                    expression. Additionally, we identified WNT10B and FGF2 as dorsal- and ventral-mediated signals, respectively, that create the inductive environment for\n                    <jats:italic>Shh<\/jats:italic>\n                    expression. Our findings clarify the role of dorsal and ventral cells in inducing\n                    <jats:italic>Shh<\/jats:italic>\n                    , a mechanism that has rarely been studied in the context of limb regeneration and pattern formation. This model provides new insights into how cells with different positional identities drive the regeneration process.\n                  <\/jats:p>","DOI":"10.7554\/elife.106917","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T10:30:49Z","timestamp":1748601049000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.106917","source":"Crossref","is-referenced-by-count":2,"title":["Dorsoventral-mediated Shh induction is required for axolotl limb regeneration"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6539-989X","authenticated-orcid":true,"given":"Sakiya","family":"Yamamoto","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pc6pc55","id-type":"ROR","asserted-by":"publisher"}],"name":"Okayama University, Graduate School of Environmental, Life, Natural Science and Technology","place":["Okayama, 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Science and Technology","place":["Okayama, Japan"]},{"id":[{"id":"https:\/\/ror.org\/02pc6pc55","id-type":"ROR","asserted-by":"publisher"}],"name":"Ushimado Marine Institute (UMI), Okayama University","place":["Okayama, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9821-4290","authenticated-orcid":true,"given":"Akira","family":"Satoh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pc6pc55","id-type":"ROR","asserted-by":"publisher"}],"name":"Okayama University, Graduate School of Environmental, Life, Natural Science and Technology","place":["Okayama, 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RNA-seq of dorsally and ventrally blastemas induced by accessory limb model (ALM) at 10 days post surgery. DNA Data Bank of Japan (DDBJ). https:\/\/ddbj.nig.ac.jp\/search\/entry\/bioproject\/PRJDB38065. PRJDB38065."},{"key":"dataset2","type":"dataset","article-title":"blastema 7dpa","volume-title":"NCBI Sequence Read Archive","author":"Li","year":"2021","unstructured":"Li H, Wei X, Zhou L, Zhang W, Wang C, Guo Y, Li D, Chen J, Liu T, Zhang Y, Ma S, Wang C, Tan F, Xu J, Liu Y, Yuan Y, Chen L, Wang Q, Qu J, Shen Y, Liu S, Fan G, Liu L, Liu X, Hou Y, Liu GH, Gu Y, Xu X. 2021. blastema 7dpa. NCBI Sequence Read Archive. https:\/\/www.ncbi.nlm.nih.gov\/sra\/SRX7140465. 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