Phenotypic models of complex developmental paradigms

22 March 2013

Eric Siggia
Center for Studies in Physics and Biology
Rockefeller University


I am interested in the spatial-temporal aspects of development and cell signaling pathways. Most of the classical systems involve several interacting signaling pathways and dozens of genes, which renders gene centric models impossible to implement quantitatively. Recently Corson and Siggia [1] modeled vulva patterning in C. elegans by representing the EGF and N pathways by only two variables/cell but embedded in a nonlinear system consistent with the developmental outcomes. This model could be largely fit to genetic and cell ablation data that specify partially penetrant phenotypes. Several experiments that purported to show pathway epistasis were explained by the simple addition of vectors representing the pathways, filtered through the underlying nonlinear dynamics of the model. Geometric models are the natural way to quantify time dependent phenotypes such as development. Applications to Hox patterning and somitogenesis were reviewed by François and Siggia [2]. This reduces the visionary ideas of Waddington to practical engineering.


  1. F Corson, E D Siggia, "Geometry, epistasis, and developmental patterning", PNAS 109:5568-75 2012. PubMed
  2. P François, E D Siggia, "Phenotypic models of evolution and development: geometry as destiny", Curr Opin Genet Dev 22:627-33 2012. PubMed

current theory lunch schedule