{"data":{"id":"10.25384/sage.c.4123457.v1","type":"dois","attributes":{"doi":"10.25384/sage.c.4123457.v1","prefix":"10.25384","suffix":"sage.c.4123457.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"M. Nakatomi","affiliation":[],"nameIdentifiers":[]},{"name":"H. Ida-Yonemochi","affiliation":[],"nameIdentifiers":[]},{"name":"C. Nakatomi","affiliation":[],"nameIdentifiers":[]},{"name":"K. Saito","affiliation":[],"nameIdentifiers":[]},{"name":"S. Kenmotsu","affiliation":[],"nameIdentifiers":[]},{"name":"R.L. Maas","affiliation":[],"nameIdentifiers":[]},{"name":"H. Ohshima","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"\u003ci\u003eMsx2\u003c/i\u003e Prevents Stratified Squamous Epithelium Formation in the Enamel Organ"}],"publisher":"Figshare","container":{},"publicationYear":2018,"subjects":[{"subject":"110599 Dentistry not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"91299 Materials Engineering not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Materials engineering","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2018-06-05","dateType":"Created"},{"date":"2018-06-05","dateType":"Updated"},{"date":"2018","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1177/0022034518777746","relatedIdentifierType":"DOI"},{"relationType":"IsIdenticalTo","relatedIdentifier":"10.25384/sage.c.4123457","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"CC BY 4.0","rightsUri":"https://creativecommons.org/licenses/by/4.0"}],"descriptions":[{"description":"Tooth enamel is manufactured by the inner enamel epithelium of the multilayered enamel organ. \u003ci\u003eMsx2\u003c/i\u003e loss-of-function mutation in a mouse model causes an abnormal accumulation of epithelial cells in the enamel organ, but the underlying mechanism by which \u003ci\u003eMsx2\u003c/i\u003e regulates amelogenesis is poorly understood. We therefore performed detailed histological and molecular analyses of \u003ci\u003eMsx2\u003c/i\u003e null mice. \u003ci\u003eMsx2\u003c/i\u003e null ameloblasts and stratum intermedium (SI) cells differentiated normally in the early stages of amelogenesis. However, during subsequent developmental stages, the outer enamel epithelium (OEE) became highly proliferative and transformed into a keratinized stratified squamous epithelium that ectopically expressed stratified squamous epithelium markers, including Heat shock protein 25, Loricrin, and Keratin 10. Moreover, expression of hair follicle–specific keratin genes such as \u003ci\u003eKeratin 26\u003c/i\u003e and \u003ci\u003eKeratin 73\u003c/i\u003e was upregulated in the enamel organ of \u003ci\u003eMsx2\u003c/i\u003e mutants. With the accumulation of keratin in the stellate reticulum (SR) region and subsequent odontogenic cyst formation, SI cells gradually lost the ability to differentiate, and the expression of Sox2 and Notch1 was downregulated, leading to ameloblast depolarization. As a consequence, the organization of the \u003ci\u003eMsx2\u003c/i\u003e mutant enamel organ became disturbed and enamel failed to form in the normal location. Instead, there was ectopic mineralization that likely occurred within the SR. In summary, we show that during amelogenesis, \u003ci\u003eMsx2\u003c/i\u003e executes a bipartite function, repressing the transformation of OEE into a keratinized stratified squamous epithelium while simultaneously promoting the development of a properly differentiated enamel organ competent for enamel formation.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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","url":"https://figshare.com/collections/_i_Msx2_i_Prevents_Stratified_Squamous_Epithelium_Formation_in_the_Enamel_Organ/4123457/1","contentUrl":null,"metadataVersion":1,"schemaVersion":"http://datacite.org/schema/kernel-3","source":"api","isActive":true,"state":"findable","reason":null,"viewCount":0,"viewsOverTime":[],"downloadCount":0,"downloadsOverTime":[],"referenceCount":1,"citationCount":0,"citationsOverTime":[],"partCount":0,"partOfCount":0,"versionCount":0,"versionOfCount":0,"created":"2018-06-05T11:02:30.000Z","registered":"2018-06-05T11:02:30.000Z","published":"2018","updated":"2024-08-28T05:40:49.000Z"},"relationships":{"client":{"data":{"id":"sage.journals","type":"clients"}},"provider":{"data":{"id":"sage","type":"providers"}},"media":{"data":{"id":"10.25384/sage.c.4123457.v1","type":"media"}},"references":{"data":[{"id":"10.1177/0022034518777746","type":"dois"}]},"citations":{"data":[]},"parts":{"data":[]},"partOf":{"data":[]},"versions":{"data":[]},"versionOf":{"data":[]}}}}