Bistability, Bifurcations, and Waddington's Epigenetic Landscape

• Published in: Current biology Vol. 22; no. 11; pp. R458 - R466
• Main Author: Ferrell, James E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 05.06.2012
• Subjects: Animals; Cell Differentiation; Developmental Biology; Epigenesis, Genetic; epigenetics; landscapes; Models, Biological; valleys
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2012.03.045

Waddington's epigenetic landscape is probably the most famous and most powerful metaphor in developmental biology. Cells, represented by balls, roll downhill through a landscape of bifurcating valleys. Each new valley represents a possible cell fate and the ridges between the valleys maintain the cell fate once it has been chosen. Here I examine models of two important developmental processes — cell-fate induction and lateral inhibition — and ask whether the landscapes for these models at least qualitatively resemble Waddington's picture. For cell-fate induction, the answer is no. The commitment of a cell to a new fate corresponds to the disappearance of a valley from the landscape, not the splitting of one valley into two, and it occurs through a type of bifurcation — a saddle-node bifurcation — that possesses an intrinsic irreversibility that is missing from Waddington's picture. Lateral inhibition, a symmetrical cell–cell competition process, corresponds better to Waddington's picture, with one valley reversibly splitting into two through a pitchfork bifurcation. I propose an alternative epigenetic landscape that has numerous valleys and ridges right from the start, with the process of cell-fate commitment corresponding to the irreversible disappearance of some of these valleys and ridges, via cell-fate induction, complemented by the creation of new valleys and ridges through processes like cell–cell competition.