{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:12:10Z","timestamp":1771467130959,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K07772"],"award-info":[{"award-number":["21K07772"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26220004"],"award-info":[{"award-number":["26220004"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cortical plate (CP) first appears at seven postconceptional weeks (pcw), when it splits the preexisting preplate into two layers, the marginal zone and the presubplate (pSP). Although three\u2010dimensional (3D) analysis using fetal magnetic resonance imaging and two\u2010dimensional tissue observations have been reported, there have been no studies analyzing the early development of the layer structure corresponding to the pSP stage in 3D. Here, we reconstructed 3\u2010D models of the brain with a focus on the cortical layers in pSP stage. To achieve this, we digitized serial tissue sections of embryos between CS20 and CS23 from the Kyoto Collection (<jats:italic>n<\/jats:italic>\u00a0=\u00a07, approximately 7\u20138.5 pcw), and specimens at early fetal phase from the Blechschmidt Collection (<jats:italic>n<\/jats:italic>\u00a0=\u00a02, approximately 9.5\u201312 pcw, crown rump length [CRL] 39 and 64\u00a0mm). We observed tissue sections and 3D images and performed quantitative analysis of the thickness, surface area, and volume. Because the boundary between pSP and the intermediate zone (IZ) could not be distinguished in hematoxylin and eosin\u2010stained sections, the two layers were analyzed together as a single layer in this study. The histology of the layers was observed from CS21 and became distinct at CS22. Subsequently, we observed the 3\u2010D models; pSP\u2010IZ was present in a midlateral region of the cerebral wall at CS21, and an expansion centered around this region was observed after CS22. We observed it over the entire cerebral hemisphere at early fetal phase (CRL 39\u00a0mm). The thickness of pSP\u2010IZ was visible in 3D and was greater in the midlateral region. At the end of the pSP stage (CRL 64\u00a0mm), the thick region expanded to lateral, superior, and posterior regions around the primordium of the insula. While, the region near the basal ganglia was not included in the thickest 10% of the pSP\u2010IZ area. Middle cerebral artery was found in the midlateral region of the cerebral wall, near the area where pSP\u2010IZ was observed. Feature of layer structure growth was revealed by quantitative assessment as thickness, surface area, and volume. The maximum thickness value of pSP\u2010IZ and CP increased significantly according to CRL, whereas the median value increased slightly. The layer structure appeared to grow and spread thin, rather than thickening during early development, which is characteristic during pSP stages. The surface area of the cerebral total tissue, CP, and pSP\u2010IZ increased in proportion to the square of CRL. The surface area of CP and pSP\u2010IZ approached that of the total tissue at the end of the pSP stage. Volume of each layer increased in proportion to the cube of CRL. pSP\u2010IZ and CP constituted over 50% of the total tissue in volume at the end of the pSP stages. We could visualize the growth of pSP\u2010IZ in 3D and quantify it during pSP stage. Our approach allowed us to observe the process of rapid expansion of pSP\u2010IZ from the midlateral regions of the cerebral wall, which subsequently becomes the insula.<\/jats:p>","DOI":"10.1111\/joa.13488","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T03:50:07Z","timestamp":1623988207000},"page":"1039-1049","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Early development of the cortical layers in the human brain"],"prefix":"10.1111","volume":"239","author":[{"given":"Mei","family":"Terashima","sequence":"first","affiliation":[{"name":"Human Health Science, Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aoi","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Human Health Science, Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"M\u00e4nner","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Embryology UMG Georg\u2010August\u2010University of G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-6927","authenticated-orcid":false,"given":"Shigehito","family":"Yamada","sequence":"additional","affiliation":[{"name":"Human Health Science, Graduate School of Medicine Kyoto University Kyoto Japan"},{"name":"Congenital Anomaly Research Center Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-9384","authenticated-orcid":false,"given":"Tetsuya","family":"Takakuwa","sequence":"additional","affiliation":[{"name":"Human Health Science, Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy327"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781420003277"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.5772\/38764"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-010-0286-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.23794"},{"issue":"1","key":"e_1_2_10_7_1","first-page":"216","article-title":"Neurexins 1\u20133 each have a distinct pattern of expression in the early developing human cerebral cortex","volume":"27","author":"Harkin L.F.","year":"2017","journal-title":"Cerebral 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