title: Bone morphogenic protein signalling suppresses differentiation of pluripotent cells by maintaining expression of E-Cadherin.
abstract: Bone morphogenic protein (BMP) signalling contributes towards maintenance of pluripotency and favours mesodermal over neural fates upon differentiation, but the mechanisms by which BMP controls differentiation are not well understood. We report that BMP regulates differentiation by blocking downregulation of Cdh1, an event that accompanies the earliest stages of neural and mesodermal differentiation. We find that loss of Cdh1 is a limiting requirement for differentiation of pluripotent cells, and that experimental suppression of Cdh1 activity rescues the BMP-imposed block to differentiation. We further show that BMP acts prior to and independently of Cdh1 to prime pluripotent cells for mesoderm differentiation, thus helping to reinforce the block to neural differentiation. We conclude that differentiation depends not only on exposure to appropriate extrinsic cues but also on morphogenetic events that control receptivity to those differentiation cues, and we explain how a key pluripotency signal, BMP, feeds into this control mechanism. DOI: http://dx.doi.org/10.7554/eLife.01197.001.
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Mattias
authors.initials: M
authors.lastname: Malaguti
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nistor
authors.forename: Guillaume
authors.initials: G
authors.lastname: Blin
authors.forename: Amy
authors.initials: A
authors.lastname: Pegg
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Zhou
authors.forename: Sally
authors.initials: S
authors.lastname: Lowell
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins; D015820:Cadherins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1
keywords: BMP; Cdh1; Id1; Pluripotent stem cells