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With most of the current models and evidence addressing secondary folds, we sought to focus on the global geometry of the mature brain by studying its most distinctive feature, the Sylvian fissure. A digital human fetal brain atlas was developed using previously obtained MRI imaging of 81 healthy fetuses between gestational ages 21 and 38\u00a0weeks. To account for the development of the Sylvian fissure, we compared the growth of the frontotemporal opercula over the insular cortex and compared the transcriptome of the developing cortices for both regions. Spatiotemporal mapping of the lateral hemispheric surface showed the highest rate of organized growth in regions bordering the Sylvian fissure of the frontal, parietal and temporal lobes. Volumetric changes were first observed in the posterior aspect of the fissure moving anteriorly to the frontal lobe and laterally in the direction of the temporal pole. The insular region, delineated by the limiting insular gyri, expanded to a much lesser degree. The gene expression profile, before folding begins in the maturing brain, was significantly different in the developing opercular cortex compared to the insula. The Sylvian fissure forms by the relative overgrowth of the frontal and temporal lobes over the insula, corresponding to domains of highly expressed transcription factors involved in neuroepithelial cell differentiation.<\/jats:p>","DOI":"10.1038\/s41598-020-71535-4","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T10:03:28Z","timestamp":1599041008000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sylvian fissure development is linked to differential genetic expression in the pre-folded brain"],"prefix":"10.1038","volume":"10","author":[{"given":"Arka N.","family":"Mallela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa K.","family":"Brisbin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Bush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Goldschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"71535_CR1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/ana.410010109","volume":"1","author":"JG Chi","year":"1977","unstructured":"Chi, J. 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