Fumiya Meguro, Katsushige Kawasaki, Yoshito Kakihara, Maiko Kawasaki, Makoto Fukushima, Finsa Tisna Sari, Vanessa Utama, Alex Kesuma, Jun Nihara, Takehisa Kudo, Akira Fujita, Kaya Ichikawa, Kazuaki Osawa, Takeyasu Maeda, Koichi Tabeta, Makio Saeki, Atsushi Ohazama
{"title":"胚胎表皮分层过程中的DNA修复。","authors":"Fumiya Meguro, Katsushige Kawasaki, Yoshito Kakihara, Maiko Kawasaki, Makoto Fukushima, Finsa Tisna Sari, Vanessa Utama, Alex Kesuma, Jun Nihara, Takehisa Kudo, Akira Fujita, Kaya Ichikawa, Kazuaki Osawa, Takeyasu Maeda, Koichi Tabeta, Makio Saeki, Atsushi Ohazama","doi":"10.1002/dvdy.70046","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Genomes are constantly exposed to a myriad of DNA-damaging agents. Robust DNA repair mechanisms protect DNA by removing or tolerating damage. However, it remains unclear whether these mechanisms are required for organogenesis.</p><p><strong>Results: </strong>Multiple epithelial layers are essential for skin function, including body protection. The epidermis is initiated as a single layer and then stratifies in utero. Stratification did not occur in mice with epithelial conditional deletion of the DNA repair molecule Reptin (Reptin<sup>fl/fl</sup>;K14Cre). DNA damage was observed in the mutant epidermis but not in the wild-type epidermis. The mutant epidermis also showed reduced cell proliferation and upregulated p53 expression. Stratification was restored when p53 was deleted in the Reptin mutant mice by generating Reptin and p53 double mutant mice (Reptin<sup>fl/fl</sup>;K14Cre;p53<sup>-/-</sup>).</p><p><strong>Conclusion: </strong>In the wild-type epidermis, DNA is likely damaged at the initiation of embryonic stratification and promptly repaired by DNA repair mechanisms involving Reptin.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"DNA repair during embryonic epidermal stratification.\",\"authors\":\"Fumiya Meguro, Katsushige Kawasaki, Yoshito Kakihara, Maiko Kawasaki, Makoto Fukushima, Finsa Tisna Sari, Vanessa Utama, Alex Kesuma, Jun Nihara, Takehisa Kudo, Akira Fujita, Kaya Ichikawa, Kazuaki Osawa, Takeyasu Maeda, Koichi Tabeta, Makio Saeki, Atsushi Ohazama\",\"doi\":\"10.1002/dvdy.70046\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Genomes are constantly exposed to a myriad of DNA-damaging agents. Robust DNA repair mechanisms protect DNA by removing or tolerating damage. However, it remains unclear whether these mechanisms are required for organogenesis.</p><p><strong>Results: </strong>Multiple epithelial layers are essential for skin function, including body protection. The epidermis is initiated as a single layer and then stratifies in utero. Stratification did not occur in mice with epithelial conditional deletion of the DNA repair molecule Reptin (Reptin<sup>fl/fl</sup>;K14Cre). DNA damage was observed in the mutant epidermis but not in the wild-type epidermis. The mutant epidermis also showed reduced cell proliferation and upregulated p53 expression. Stratification was restored when p53 was deleted in the Reptin mutant mice by generating Reptin and p53 double mutant mice (Reptin<sup>fl/fl</sup>;K14Cre;p53<sup>-/-</sup>).</p><p><strong>Conclusion: </strong>In the wild-type epidermis, DNA is likely damaged at the initiation of embryonic stratification and promptly repaired by DNA repair mechanisms involving Reptin.</p>\",\"PeriodicalId\":11247,\"journal\":{\"name\":\"Developmental Dynamics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Developmental Dynamics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/dvdy.70046\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Dynamics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/dvdy.70046","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
DNA repair during embryonic epidermal stratification.
Background: Genomes are constantly exposed to a myriad of DNA-damaging agents. Robust DNA repair mechanisms protect DNA by removing or tolerating damage. However, it remains unclear whether these mechanisms are required for organogenesis.
Results: Multiple epithelial layers are essential for skin function, including body protection. The epidermis is initiated as a single layer and then stratifies in utero. Stratification did not occur in mice with epithelial conditional deletion of the DNA repair molecule Reptin (Reptinfl/fl;K14Cre). DNA damage was observed in the mutant epidermis but not in the wild-type epidermis. The mutant epidermis also showed reduced cell proliferation and upregulated p53 expression. Stratification was restored when p53 was deleted in the Reptin mutant mice by generating Reptin and p53 double mutant mice (Reptinfl/fl;K14Cre;p53-/-).
Conclusion: In the wild-type epidermis, DNA is likely damaged at the initiation of embryonic stratification and promptly repaired by DNA repair mechanisms involving Reptin.
期刊介绍：
Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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