Gene-free methodology for cell fate dynamics during development

Abstract

Models of cell function that assign a variable to each gene frequently lead to systems of equations with many parameters whose behavior is obscure. Geometric models reduce dynamics to intuitive pictorial elements that provide compact representations for sparse in vivo data and transparent descriptions of developmental transitions. To illustrate, a geometric model fit to vulval development in Caenorhabditis elegans, implies a phase diagram where cell-fate choices are displayed in a plane defined by EGF and Notch signaling levels. This diagram defines allowable and forbidden cell-fate transitions as EGF or Notch levels change, and explains surprising observations previously attributed to context-dependent action of these signals. The diagram also reveals the existence of special points at which minor changes in signal levels lead to strong epistatic interactions between EGF and Notch. Our model correctly predicts experiments near these points and suggests specific timed perturbations in signals that can lead to additional unexpected outcomes.