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Here, we identify a pivotal role of fatty acid synthase (FASN)-dependent de novo lipogenesis for mouse and human brain development, as genetic deletion of FASN leads to microcephaly in the developing mouse cortex and cortical malformations in human embryonic stem cell\u2013derived forebrain organoids. Mechanistically, we show that FASN is required for proper polarity of apical progenitor cells. The dual approach applied here, using mouse genetics and human forebrain organoids, establishes a role of FASN-dependent lipogenesis for mouse and human brain development and identifies a link between progenitor-cell polarity and lipid metabolism.<\/jats:p>","DOI":"10.1073\/pnas.2112040119","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T16:00:40Z","timestamp":1641571240000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["FASN-dependent de novo lipogenesis is required for brain development"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-6372","authenticated-orcid":false,"given":"Daniel","family":"Gonzalez-Bohorquez","sequence":"first","affiliation":[{"name":"Laboratory of Neural Plasticity, Faculties of Medicine and Science, Brain Research Institute, University of Zurich 8057 Zurich, 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