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However, our recent study suggested that the premaxilla, the rostralmost upper jaw bone, was rearranged during the evolution of therian mammals, being replaced by the septomaxilla at least in the lateral part. In the present study, to understand more about the process of evolution from the ancestral upper jaw to the therian face, we re\u2010examined the development of the therian premaxilla (incisive bone). By comparing mouse, bat, goat, and cattle fetuses, we confirmed that the therian premaxilla has dual developmental origins, the lateral body and the palatine process. This dual development is widely conserved among the therian mammals. Cell\u2010lineage\u2010tracing experiments using<jats:italic>Dlx1<\/jats:italic>\u2010CreER<jats:sup>T2<\/jats:sup>mice revealed that the palatine process arises in the ventral part of the premandibular domain, where the nasopalatine nerve distributes, whereas the lateral body develops from the maxillary prominence in the domain of the maxillary nerve. Through comparative analysis using various tetrapods, we concluded that the palatine process should not be considered part of the ancestral premaxilla. It rather corresponds to the anterior region of the vomerine bone of nonmammalian tetrapods. Thus, the present findings indicate that the true premaxilla was completely lost during the evolution of the therian mammals, resulting in the establishment of the unique therian face as an evolutionary novelty. Reconsideration of the homological framework of the cranial skeleton based on the topographical relationships of the ossification center during embryonic development is warranted.<\/jats:p>","DOI":"10.1111\/ede.12417","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T07:39:52Z","timestamp":1661499592000},"page":"103-118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evolution of the therian face through complete loss of the premaxilla"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1324-8139","authenticated-orcid":false,"given":"Hiroki","family":"Higashiyama","sequence":"first","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Koyabu","sequence":"additional","affiliation":[{"name":"Research and Development Center for Precision Medicine University of Tsukuba Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine The University of Tokyo Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"207","article-title":"Die morphologische Bedeutung der seitlichen Kieferspalte und die wahrscheinliche Existenz von 4 Zwischenkiefern bei den S\u00e4ugern","volume":"2","author":"Albrecht P.","year":"1879","journal-title":"Zoologischer Anzeiger"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(99)00023-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/9783110341553-005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/azo.12131"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-003-0366-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.20804"},{"key":"e_1_2_9_8_1","unstructured":"Biondi D.(1886).Ueber Zwischenkiefer und Lippenkiefer\u2010Gaumenspalte.Archiv f\u00fcr Anatomie und Physiologie 550\u2013555."},{"key":"e_1_2_9_9_1","first-page":"477","article-title":"On the homology of the palatine process of the mammalian premaxillary","volume":"10","author":"Broom R.","year":"1895","journal-title":"Proceedings of the Linnean Society of New South Wales"},{"key":"e_1_2_9_10_1","first-page":"189","volume-title":"Great transformations in vertebrate evolution","author":"Crompton A.","year":"2015"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/02724634.2017.1269116"},{"key":"e_1_2_9_12_1","volume-title":"The development of the vertebrate skull","author":"Beer S. 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