Dhruv Raina, Azra Bahadori,* Angel Stanoev,‡ Michelle Protzek, Aneta Koseska,§ and Christian Schröter**
"Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
*Present address: Center for Chromosome Stability, University of Copenhagen, 2200 Copenhagen N, Denmark.
‡Present address: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
§Present address: Cellular Computations and Learning, Research Center Caesar, 53175 Bonn, Germany.
¶These authors contributed equally to this work
** Author for correspondence ([email protected])
Handling Editor: James Briscoe"
"During embryonic development and tissue homeostasis, reproducible proportions of differentiated cell types are specified from populations of multipotent precursor cells. Molecular mechanisms that enable both robust cell-type proportioning despite variable initial conditions in the precursor cells, and the re-establishment of these proportions upon perturbations in a developing tissue remain to be characterized. Here, we report that the differentiation of robust proportions of epiblast-like and primitive endoderm-like cells in mouse embryonic stem cell cultures emerges at the population level through cell-cell communication via a short-range fibroblast growth factor 4 (FGF4) signal. We characterize the molecular and dynamical properties of the communication mechanism and show how it controls both robust cell-type proportioning from a wide range of experimentally controlled initial conditions, as well as the autonomous re-establishment of these proportions following the isolation of one cell type. The generation and maintenance of reproducible proportions of discrete cell types is a new function for FGF signaling that might operate in a range of developing tissues.
KEY WORDS: FGF signaling, Embryonic stem cells, Preimplantation development, Primitive endoderm, Epiblast, Dynamical system, Mouse
DOI: https://dx.doi.org/ 10.1242/dev.199926
Time-lapse imaging was started within 2 h after sorting on an Olympus IX81 widefield microscope equipped with LED illumination (pE4000, CoolLED) and a Hamamatsu c9100-13 EMCCD camera.
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The pE-4000 Universal Illumination System offers 16 selectable wavelengths from 365 - 770 nm, making it a highly flexible illuminator covering a wide variety of fluorophores
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