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"


Cell Biology


"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: 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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