Edinburgh Research Explorer

PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix.

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions



  • Download as Adobe PDF

    Rights statement: This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

    Final published version, 4.83 MB, PDF document

Original languageEnglish
Article numbere00806
Issue number2
Publication statusPublished - 24 Dec 2013


During embryonic development signalling pathways act repeatedly in different contexts to pattern the emerging germ layers. Understanding how these different responses are regulated is a central question for developmental biology. In this study, we used mouse embryonic stem cell (mESC) differentiation to uncover a new mechanism for PI3K signalling that is required for endoderm specification. We found that PI3K signalling promotes the transition from naïve endoderm precursors into committed anterior endoderm. PI3K promoted commitment via an atypical activity that delimited epithelial-to-mesenchymal transition (EMT). Akt1 transduced this activity via modifications to the extracellular matrix (ECM) and appropriate ECM could itself induce anterior endodermal identity in the absence of PI3K signalling. PI3K/Akt1-modified ECM contained low levels of Fibronectin (Fn1) and we found that Fn1 dose was key to specifying anterior endodermal identity in vivo and in vitro. Thus, localized PI3K activity affects ECM composition and ECM in turn patterns the endoderm.

Download statistics

No data available

ID: 12306836