PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix
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) differentiatio...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2013-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/00806 |
| _version_ | 1811180481099595776 |
|---|---|
| author | S Nahuel Villegas Michaela Rothová Martin E Barrios-Llerena Maria Pulina Anna-Katerina Hadjantonakis Thierry Le Bihan Sophie Astrof Joshua M Brickman |
| author_facet | S Nahuel Villegas Michaela Rothová Martin E Barrios-Llerena Maria Pulina Anna-Katerina Hadjantonakis Thierry Le Bihan Sophie Astrof Joshua M Brickman |
| author_sort | S Nahuel Villegas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:03:50Z |
| format | Article |
| id | doaj.art-76c156f45d0a4ed5ade068a0a524dd7f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:03:50Z |
| publishDate | 2013-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-76c156f45d0a4ed5ade068a0a524dd7f2022-12-22T04:32:41ZengeLife Sciences Publications LtdeLife2050-084X2013-12-01210.7554/eLife.00806PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrixS Nahuel Villegas0Michaela Rothová1Martin E Barrios-Llerena2Maria Pulina3Anna-Katerina Hadjantonakis4Thierry Le Bihan5Sophie Astrof6Joshua M Brickman7Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom; The Danish Stem Cell Center (DanStem), University of Copenhagen, Copenhagen, DenmarkThe Danish Stem Cell Center (DanStem), University of Copenhagen, Copenhagen, DenmarkCentre for Synthetic and Systems Biology (SynthSys), University of Edinburgh, Edinburgh, United KingdomDevelopmental Biology Program, Sloan-Kettering Institute, New York, United States; Center for Translational Medicine, Jefferson Medical College, Philadelphia, United StatesDevelopmental Biology Program, Sloan-Kettering Institute, New York, United StatesCentre for Synthetic and Systems Biology (SynthSys), University of Edinburgh, Edinburgh, United KingdomCenter for Translational Medicine, Jefferson Medical College, Philadelphia, United StatesInstitute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom; The Danish Stem Cell Center (DanStem), University of Copenhagen, Copenhagen, DenmarkDuring 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.https://elifesciences.org/articles/00806extracellular matrixFibronectinPI3K/Akt1endodermproteomicsforegut |
| spellingShingle | S Nahuel Villegas Michaela Rothová Martin E Barrios-Llerena Maria Pulina Anna-Katerina Hadjantonakis Thierry Le Bihan Sophie Astrof Joshua M Brickman PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix eLife extracellular matrix Fibronectin PI3K/Akt1 endoderm proteomics foregut |
| title | PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix |
| title_full | PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix |
| title_fullStr | PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix |
| title_full_unstemmed | PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix |
| title_short | PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix |
| title_sort | pi3k akt1 signalling specifies foregut precursors by generating regionalized extra cellular matrix |
| topic | extracellular matrix Fibronectin PI3K/Akt1 endoderm proteomics foregut |
| url | https://elifesciences.org/articles/00806 |
| work_keys_str_mv | AT snahuelvillegas pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT michaelarothova pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT martinebarriosllerena pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT mariapulina pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT annakaterinahadjantonakis pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT thierrylebihan pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT sophieastrof pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix AT joshuambrickman pi3kakt1signallingspecifiesforegutprecursorsbygeneratingregionalizedextracellularmatrix |