Emergence and patterning dynamics of mouse-definitive endoderm
Maayan Pour,
Abhishek Sampath Kumar,
Naama Farag,
Adriano Bolondi,
Helene Kretzmer,
Maria Walther,
Lars Wittler,
Alexander Meissner,
Iftach Nachman
Affiliations
Maayan Pour
School of Neurobiology, Biochemistry and Biophysics, Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 6997801, Israel
Abhishek Sampath Kumar
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
Naama Farag
School of Neurobiology, Biochemistry and Biophysics, Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 6997801, Israel
Adriano Bolondi
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
Helene Kretzmer
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
Maria Walther
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
Lars Wittler
Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
Alexander Meissner
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Iftach Nachman
School of Neurobiology, Biochemistry and Biophysics, Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 6997801, Israel; Corresponding author
Summary: The segregation of definitive endoderm (DE) from bipotent mesendoderm progenitors leads to the formation of two distinct germ layers. Dissecting DE commitment and onset has been challenging as it occurs within a narrow spatiotemporal window in the embryo. Here, we employ a dual Bra/Sox17 reporter cell line to study DE onset dynamics. We find Sox17 expression initiates in vivo in isolated cells within a temporally restricted window. In 2D and 3D in vitro models, DE cells emerge from mesendoderm progenitors at a temporally regular, but spatially stochastic pattern, which is subsequently arranged by self-sorting of Sox17 + cells. A subpopulation of Bra-high cells commits to a Sox17+ fate independent of external Wnt signal. Self-sorting coincides with upregulation of E-cadherin but is not necessary for DE differentiation or proliferation. Our in vivo and in vitro results highlight basic rules governing DE onset and patterning through the commonalities and differences between these systems.
