A wave of WNT signaling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells

Development
I. MartynEric D Siggia

Abstract

Long-range signaling by morphogens and their inhibitors define embryonic patterning yet quantitative data and models are rare, especially in humans. Here, we use a human embryonic stem cell micropattern system to model formation of the primitive streak (PS) by WNT. In the pluripotent state, E-cadherin (E-CAD) transduces boundary forces to focus WNT signaling to the colony border. Following application of WNT ligand, E-CAD mediates a front or wave of epithelial-to-mesenchymal (EMT) conversion analogous to PS extension in an embryo. By knocking out the secreted WNT inhibitors active in our system, we show that DKK1 alone controls the extent and duration of patterning. The NODAL inhibitor cerberus 1 acts downstream of WNT to refine the endoderm versus mesoderm fate choice. Our EMT wave is a generic property of a bistable system with diffusion and we present a single quantitative model that describes both the wave and our knockout data.

References

Nov 15, 2002·Developmental Cell·Federica Bertocchini, Claudio D Stern
Mar 6, 2004·Science·W James Nelson, Roel Nusse
Oct 14, 2004·Development Genes and Evolution·Jan IdkowiakChristoph Viebahn
Oct 21, 2006·Nature Biotechnology·Kevin A D'AmourEmmanuel E Baetge
Mar 28, 2007·Nature Reviews. Genetics·Patrick P L Tam, David A F Loebel
Jan 15, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Lionel F Jaffe
Apr 12, 2008·Development·Samara L LewisPatrick P L Tam
Jan 9, 2009·Nature Reviews. Molecular Cell Biology·Sebastian J Arnold, Elizabeth J Robertson
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Ken M Cadigan, Mark Peifer
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Alexander Aulehla, Olivier Pourquié
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Julian Heuberger, Walter Birchmeier
Apr 20, 2011·Current Topics in Developmental Biology·Emmanuel Farge
Dec 16, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Margot WilliamsAnn Sutherland
May 24, 2012·The EMBO Journal·Tomas ValentaKonrad Basler
Oct 2, 2012·Cold Spring Harbor Perspectives in Biology·Ken M Cadigan, Marian L Waterman
Oct 23, 2012·Cold Spring Harbor Perspectives in Biology·Cristina-Maria Cruciat, Christof Niehrs
Jan 5, 2013·Science·Le CongFeng Zhang
Jul 19, 2013·Nature·Jeremy B Chang, James E Ferrell
Jun 30, 2014·Nature Methods·Aryeh WarmflashAli H Brivanlou
Sep 23, 2014·Current Opinion in Cell Biology·Rik DerynckKoy Y Saeteurn
Oct 11, 2014·Nucleic Acids Research·Eva K BrinkmanBas van Steensel
Dec 15, 2015·Cell Reports·Georgios KanellosMargaret C Frame
Jul 28, 2016·Cell Stem Cell·Laralynne PrzybylaValerie M Weaver
Oct 14, 2016·Nature Protocols·Alessia DeglincertiAryeh Warmflash
Feb 17, 2018·Proceedings of the National Academy of Sciences of the United States of America·Massimo VergassolaStefano Di Talia

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Citations

Jun 7, 2019·Science·Marta N ShahbaziMagdalena Zernicka-Goetz
Jul 3, 2019·Nature Cell Biology·Mijo SimunovicEric D Siggia
Dec 19, 2019·Frontiers in Bioengineering and Biotechnology·Pallavi Srivastava, Kristopher A Kilian
Oct 12, 2019·Development·Karolina PunovuoriSally Lowell
Mar 7, 2020·Development·James Briscoe, Katherine Brown
Oct 7, 2020·Annual Review of Cell and Developmental Biology·Claudia GerriKathy K Niakan
Nov 6, 2020·Developmental Biology·Nicola GrittiVikas Trivedi
Nov 18, 2020·Nature Materials·Jianping FuMatthias P Lutolf
Feb 16, 2021·Developmental Biology·Iain Martyn, Zev J Gartner
Jan 15, 2021·International Journal of Molecular Sciences·Margit RosnerMarkus Hengstschläger
Jan 24, 2021·Developmental Biology·Sabitri GhimireAlfonso Martinez Arias
Feb 13, 2021·Current Opinion in Cell Biology·Jordi Berenguer, Toni Celià-Terrassa
Mar 27, 2021·Stem Cell Reports·Kirstin R W MatthewsAryeh Warmflash
Mar 24, 2021·Developmental Biology·Jake Cornwall-Scoones, Magdalena Zernicka-Goetz
Dec 18, 2020·Developmental Biology·Berna SozenMagdalena Zernicka-Goetz
Dec 23, 2020·Developmental Biology·Alexandra Schauer, Carl-Philipp Heisenberg
May 13, 2021·Stem Cell Reports·Magdalena SchindlerThorsten E Boroviak
May 30, 2021·Developmental Cell·Tien Phan-EversonEric D Siggia
Jul 31, 2021·Nature Communications·Ali H Brivanlou, Norbert Gleicher
Aug 18, 2021·ELife·Kirsty Ml MackinlayMagdalena Zernicka-Goetz
Nov 15, 2021·Journal of Molecular Biology·Yunping Chen, Yue Shao

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