Figure 1.

Two landmark views of gene regulatory network (GRN) architecture. (A) Waddington landscape. A metaphorical view of development representing an organism/cell as a ball rolling down a valley. Bifurcations in the valleys represent decision points/epigenetic influences and are formed through the actions of genes and the environment, represented as pulleys and ropes beneath the landscape. (Adapted from Mitchell 2007.) (B) Britten and Davidson view on the GRN: an integrated/combinatorial view of gene regulation. (From Britten and Davidson 1969; reproduced, with permission.) In this model, developmental inducers termed sensors were linked to multiple and redundant integrators, which regulate batteries of activator RNAs (encoding both transcription factors and noncoding RNAs in our current understanding), which in turn bind in a combinatorial fashion to diverse receptors (cis-regulatory motifs) controlling producer genes that define cellular phenotype.