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We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation as well as isogenic lines had altered migratory dynamics when grafted in the mouse brain. The affected migration was linked to altered autophagy as observed\n                    <jats:italic>in vivo<\/jats:italic>\n                    with an electron microscopic analysis of grafted hNPCs, a Western blot analysis of cortical organoids, and time\u2010lapse imaging of hNPCs in the presence of bafilomycin A1. We further show that deficits in autophagy resulted in the accumulation of paxillin, a focal adhesion protein involved in cell migration. Strikingly, a single\u2010cell RNA\u2010seq analysis of hNPCs revealed similar expression levels of autophagy\u2010related genes. Bolstering AMPK\u2010dependent autophagy by metformin, an FDA\u2010approved drug, promoted migration of PH patients\u2010derived hNPCs. Our data indicate that transcription\u2010independent homeostatic modifications in autophagy contributed to the defective migratory behavior of hNPCs\n                    <jats:italic>in vivo<\/jats:italic>\n                    and suggest that modulating autophagy in hNPCs might rescue neuronal migration deficits in some forms of PH.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202216908","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T04:33:08Z","timestamp":1692765188000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metformin rescues migratory deficits of cells derived from patients with periventricular heterotopia"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-0354","authenticated-orcid":false,"given":"Cedric","family":"Bressan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Snapyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Snapyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Klaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"di Matteo","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\/0000-0002-3299-5597","authenticated-orcid":false,"given":"Barbara","family":"Treutlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0868-1010","authenticated-orcid":false,"given":"Martin","family":"Parent","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4962-0465","authenticated-orcid":false,"given":"Armen","family":"Saghatelyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"BFEMMM202216908_CR1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.devcel.2017.08.001","volume":"42","author":"M Arata","year":"2017","unstructured":"Arata M, Sugimura K, Uemura T (2017) Difference in Dachsous levels between migrating cells coordinates the direction of collective cell migration. 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