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Methods directing MN differentiation from stem cells have been developed to enable disease modelling <jats:italic>in vitro<\/jats:italic>. However, most protocols produce only a limited subset of endogenous MN subtypes. Here we demonstrate that limb-innervating lateral motor column (LMC) MNs can be efficiently generated from mouse and human embryonic stem cells through manipulation of the transcription factor Foxp1. Foxp1-programmed MNs exhibit features of medial and lateral LMC MNs including expression of specific motor pool markers and axon guidance receptors. Importantly, they preferentially project axons towards limb muscle explants <jats:italic>in vitro<\/jats:italic> and distal limb muscles <jats:italic>in vivo<\/jats:italic> upon transplantation\u2013hallmarks of <jats:italic>bona fide<\/jats:italic> LMC MNs. These results present an effective approach for generating specific MN populations from stem cells for studying MN development and disease.<\/jats:p>","DOI":"10.1038\/ncomms7778","type":"journal-article","created":{"date-parts":[[2015,4,14]],"date-time":"2015-04-14T09:47:33Z","timestamp":1429004853000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Foxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Katrina L.","family":"Adams","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Rousso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy A.","family":"Umbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bennett G.","family":"Novitch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,4,14]]},"reference":[{"key":"BFncomms7778_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/scrt476","volume":"5","author":"I Faravelli","year":"2014","unstructured":"Faravelli, I. et al. 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