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Periventricular heterotopia (PH) is a group of aetiologically heterogeneous disorders in which a subpopulation of newborn projection neurons fails to initiate their radial migration to the cortex, ultimately resulting in bands or nodules of grey matter lining the lateral ventricles. Although a number of genes have been implicated in its cause, currently they only satisfactorily explain the pathogenesis of the condition for 50% of patients. Novel gene discovery is complicated by the extreme genetic heterogeneity recently described to underlie its cause. Here, we study the neurodevelopmental role of\n                    <jats:italic>endothelin\u2010converting enzyme\u20102<\/jats:italic>\n                    (\n                    <jats:italic>ECE2<\/jats:italic>\n                    ) for which two biallelic variants have been identified in two separate patients with PH. Our results show that manipulation of\n                    <jats:italic>ECE2<\/jats:italic>\n                    levels in human cerebral organoids and in the developing mouse cortex leads to ectopic localisation of neural progenitors and neurons. We uncover the role of\n                    <jats:italic>ECE2<\/jats:italic>\n                    in neurogenesis, and mechanistically, we identify its involvement in the generation and secretion of extracellular matrix proteins in addition to cytoskeleton and adhesion.\n                  <\/jats:p>","DOI":"10.15252\/embr.201948204","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T08:42:19Z","timestamp":1588754539000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["ECE2 regulates neurogenesis and neuronal migration during human cortical development"],"prefix":"10.1038","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4539-9038","authenticated-orcid":false,"given":"Isabel Y","family":"Buchsbaum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Kielkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Giorgio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam C","family":"O'Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Di Giaimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kyrousi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahryar","family":"Khattak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A","family":"Sieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-6775","authenticated-orcid":false,"given":"Silvia","family":"Cappello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"BFEMBR201948204_CR1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nrm1739","volume":"6","author":"M G\u00f6tz","year":"2005","unstructured":"G\u00f6tz M, Huttner WB (2005) The cell biology of neurogenesis. 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