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To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin\u2010Cre. The <jats:italic>Cdc7<\/jats:italic><jats:sup><jats:italic>Fl\/Fl<\/jats:italic><\/jats:sup> <jats:italic>Nestin<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup> mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9\u2009days after birth and did not survive for more than 19\u2009days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in <jats:italic>Cdc7<\/jats:italic><jats:sup><jats:italic>Fl\/F l<\/jats:italic><\/jats:sup><jats:italic>Nestin<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup> mice compared to the control at E15\u201018, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication\/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.<\/jats:p>","DOI":"10.1111\/gtc.13059","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T05:36:10Z","timestamp":1692423370000},"page":"679-693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cdc7 kinase is required for postnatal brain development"],"prefix":"10.1111","volume":"28","author":[{"given":"Karin","family":"Hori","sequence":"first","affiliation":[{"name":"Genome Dynamics Project, Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"},{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Genome Dynamics Project, Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiaki","family":"Ohtaka\u2010Maruyama","sequence":"additional","affiliation":[{"name":"Developmental Neuroscience Project, Department of Brain and Neurosciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomio","family":"Ono","sequence":"additional","affiliation":[{"name":"Laboratory for Transgenic Technology, Center for Basic Technology Research Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Genome Dynamics Project, Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-5302","authenticated-orcid":false,"given":"Hisao","family":"Masai","sequence":"additional","affiliation":[{"name":"Genome Dynamics Project, Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"},{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2030"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<93::AID-GENE10>3.0.CO;2-W"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135425"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.114.165308"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.06.014"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2020.611841"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201006043"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.107"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3586"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.115.3.966-974.1973"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.66.2.352"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01239-10"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.178491.111"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1845"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00997-07"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1068288"},{"key":"e_1_2_7_18_1","first-page":"2899","article-title":"Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein","volume":"13","author":"Jackson A. 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