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Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine\/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of\n                    <jats:italic>Cilk1<\/jats:italic>\n                    results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of\n                    <jats:italic>Cilk1<\/jats:italic>\n                    in tooth development.\n                    <jats:italic>Cilk1<\/jats:italic>\n                    was found to be expressed in both the epithelial and mesenchymal compartments of developing molars.\n                    <jats:italic>Cilk1<\/jats:italic>\n                    deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as\n                    <jats:italic>Ptch1<\/jats:italic>\n                    and\n                    <jats:italic>Sostdc1<\/jats:italic>\n                    , leading to the formation of diastemal supernumerary teeth. Furthermore, in\n                    <jats:italic>Cilk1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ;PCS1\u2013MRCS1\n                    <jats:sup>\u25b3\/\u25b3<\/jats:sup>\n                    mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.\n                  <\/jats:p>","DOI":"10.1038\/s41368-025-00405-4","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:02:05Z","timestamp":1764547325000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Progressive tooth pattern changes in Cilk1-deficient mice depending on Hedgehog signaling"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0174-0812","authenticated-orcid":false,"given":"Minjae","family":"Kyeong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Kyung","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8413-8247","authenticated-orcid":false,"given":"Dinuka","family":"Adasooriya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihyeon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyeon","family":"Je","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7282-2888","authenticated-orcid":false,"given":"Seok Jun","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Bum","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1753-1900","authenticated-orcid":false,"given":"Hyuk Wan","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7389-9817","authenticated-orcid":false,"given":"Eui-Sic","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-9769","authenticated-orcid":false,"given":"Sung-Won","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"405_CR1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1600-0854.2006.00516.x","volume":"8","author":"ST Christensen","year":"2007","unstructured":"Christensen, S. 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