A geometrical model of cell fate specification in the mouse blastocyst

Development. 2024 Apr 15;151(8):dev202467. doi: 10.1242/dev.202467. Epub 2024 Apr 22.


The lineage decision that generates the epiblast and primitive endoderm from the inner cell mass (ICM) is a paradigm for cell fate specification. Recent mathematics has formalized Waddington's landscape metaphor and proven that lineage decisions in detailed gene network models must conform to a small list of low-dimensional stereotypic changes called bifurcations. The most plausible bifurcation for the ICM is the so-called heteroclinic flip that we define and elaborate here. Our re-analysis of recent data suggests that there is sufficient cell movement in the ICM so the FGF signal, which drives the lineage decision, can be treated as spatially uniform. We thus extend the bifurcation model for a single cell to the entire ICM by means of a self-consistently defined time-dependent FGF signal. This model is consistent with available data and we propose additional dynamic experiments to test it further. This demonstrates that simplified, quantitative and intuitively transparent descriptions are possible when attention is shifted from specific genes to lineages. The flip bifurcation is a very plausible model for any situation where the embryo needs control over the relative proportions of two fates by a morphogen feedback.

Keywords: Dynamical systems; Mouse blastocyst; Waddington landscape.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst* / cytology
  • Blastocyst* / metabolism
  • Cell Differentiation*
  • Cell Lineage*
  • Endoderm / cytology
  • Endoderm / metabolism
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Germ Layers / cytology
  • Germ Layers / metabolism
  • Mice
  • Models, Biological*
  • Signal Transduction


  • Fibroblast Growth Factors