Bone Morphogenic Protein signalling suppresses differentiation of pluripotent cells by maintaining expression of E-Cadherin

Mattias Malaguti, Paul Nistor, Guillaume Blin, Amy Pegg, Xinzhi Zhou, Sally Lowell

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article numbere01197
Number of pages20
JournaleLIFE
Volume2
Early online date17 Dec 2013
DOIs
Publication statusPublished - Dec 2013

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