{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:25:12Z","timestamp":1766136312561,"version":"3.48.0"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100018732","name":"Ohsumi Frontier Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Development, Growth &amp; Differentiation"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>GLI3<\/jats:italic>\n                    gene, a pivotal component of the hedgehog (HH) signaling pathway, plays a fundamental role in the development and patterning of various body structures, including the brain and limbs. Mutations in the\n                    <jats:italic>GLI3<\/jats:italic>\n                    gene, particularly in the C\u2010terminal domain, are implicated in congenital anomalies such as Greig cephalopolysyndactyly syndrome and Pallister\u2013Hall syndrome. Recent studies have also suggested an archaic human\u2010type mutation in the C\u2010terminal end, which altered downstream gene regulations and anatomical structures in mice. However, the biological effects of the disruption in the\n                    <jats:italic>Gli3<\/jats:italic>\n                    C\u2010terminal end have not been studied well. Here we report novel\n                    <jats:italic>Gli3<\/jats:italic>\n                    mutant mice with nonsense mutations in the C\u2010terminal end using CRISPR\/Cas12a\u2010mediated genome editing. Analysis of the genotype\u2013phenotype correlations has revealed that the C\u2010terminal end of\n                    <jats:italic>Gli3<\/jats:italic>\n                    is critical for functional protein synthesis; therefore, the disruption of this region causes severe abnormalities in brain and digit formation. These results provide insight into the mechanisms by which\n                    <jats:italic>GLI3<\/jats:italic>\n                    mutants can cause adverse consequences during human development or result in diverse phenotypes during evolution.\n                  <\/jats:p>","DOI":"10.1111\/dgd.70033","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T13:09:23Z","timestamp":1764680963000},"page":"479-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["C\u2010Terminal End of Gli3 Is Critical for Functional Protein Synthesis and Gli3\u2010Dependent Anatomical Development"],"prefix":"10.1111","volume":"67","author":[{"given":"Nguyen Thi My","family":"Trinh","sequence":"first","affiliation":[{"name":"Applied Biology Kyoto Institute of Technology  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sota","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Applied Biology Kyoto Institute of Technology  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ako","family":"Agata","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology Kobe University School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Tojima","sequence":"additional","affiliation":[{"name":"Applied Biology Kyoto Institute of Technology  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-9521","authenticated-orcid":false,"given":"Tadashi","family":"Nomura","sequence":"additional","affiliation":[{"name":"Applied Biology Kyoto Institute of Technology  Kyoto Japan"},{"name":"Center for Social and Biomedical Engineering Kyoto Institute of Technology  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1247361"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","unstructured":"Agata A. S.Ohtsuka R.Noji H.Gotoh K.Ono andT.Nomura.2023b.\u201cA Neanderthal\/Denisovan GLI3 Variant Contributes to Anatomical Variations in Mice. bioRxiv.\u201dhttps:\/\/doi.org\/10.1101\/2023.1107.1103.547394.","DOI":"10.1101\/2023.07.03.547394"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12952"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.9.1129"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.04.025"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.12.8143"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.62"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20545"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01033"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00540-x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1741-4520.2009.00266.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1400-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608599200"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-989-5_9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01840-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14059"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.2880"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13143410"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-383834-6.00018-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075620"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.02.029"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00443-06"}],"container-title":["Development, Growth &amp; Differentiation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dgd.70033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:14:03Z","timestamp":1766135643000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dgd.70033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":23,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/dgd.70033"],"URL":"https:\/\/doi.org\/10.1111\/dgd.70033","archive":["Portico"],"relation":{},"ISSN":["0012-1592","1440-169X"],"issn-type":[{"type":"print","value":"0012-1592"},{"type":"electronic","value":"1440-169X"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}