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In this study, we report that ablation of\n                    <jats:italic>Isl1<\/jats:italic>\n                    in the epithelium leads to complete cleft palate. A significant reduction in mesenchymal cell proliferation was detected in the\n                    <jats:italic>Isl1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Pitx2Cre<\/jats:italic>\n                    <\/jats:sup>\n                    mutant palates, but there was no significant difference in apoptosis between wild\u2010type and mutant embryos. Fewer rugae structures were observed in\n                    <jats:italic>Isl1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Pitx2Cre<\/jats:italic>\n                    <\/jats:sup>\n                    mutant embryos.\n                    <jats:italic>Shh<\/jats:italic>\n                    ,\n                    <jats:italic>Sox2<\/jats:italic>\n                    ,\n                    <jats:italic>Foxe1<\/jats:italic>\n                    ,\n                    <jats:italic>Foxd2<\/jats:italic>\n                    , and\n                    <jats:italic>Msx1<\/jats:italic>\n                    expression was downregulated in the developing palate in\n                    <jats:italic>Isl1<\/jats:italic>\n                    mutant embryos. We found that ISL1 can directly regulate\n                    <jats:italic>Shh<\/jats:italic>\n                    expression in palatal epithelial cells, suggesting a critical role for ISL1 in epithelial\u2013mesenchymal interactions during palate development. Remarkably, cleft palate defects due to\n                    <jats:italic>Isl1<\/jats:italic>\n                    deletion were rescued by a conditional transgenic allele (Tg\u2010\n                    <jats:italic>pmes<\/jats:italic>\n                    \u2010\n                    <jats:italic>Ihh<\/jats:italic>\n                    ), confirming the genetic integration of Hedgehog signaling. Our findings indicate that ISL1 controls palatal shelf morphogenesis by modulating epithelial\u2010mesenchymal communication via SHH signaling.\n                  <\/jats:p>","DOI":"10.1111\/febs.17369","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T10:59:22Z","timestamp":1734692362000},"page":"851-863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptional factor\n                    <scp>ISL<\/scp>\n                    1 regulates palate development by tuning the\n                    <scp>SHH<\/scp>\n                    cascade"],"prefix":"10.1111","volume":"292","author":[{"given":"Chujing","family":"Zhang","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences Hangzhou Normal University  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