Assessing regulatory information in developmental gene regulatory networks

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 23; pp. 5862 - 5869
• Main Authors: Peter, Isabelle S., Davidson, Eric H.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06-06-2017
• Subjects: Algorithms; Biological Sciences; Boolean algebra; Circuit design; COLLOQUIUM PAPERS; Feedback; Genes; Genetic transformation; Information retrieval; Network topologies; Positive feedback; Regulatory sequences; Sackler on Gene Regulatory Networks and Network Models in Development and Evolution; network hierarchy; network topology; Boolean modeling; circuit function; developmental GRN
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1610616114

Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory information at different levels of network organization, from single node to subcircuit to large-scale GRNs and discuss how regulatory design features such as network architecture, hierarchical organization, and cis-regulatory logic contribute to the developmental function of network circuits. Using specific subcircuits from the sea urchin endomesoderm GRN, for which both circuit design and biological function have been described, we evaluate by Boolean modeling and in silico perturbations the import of given circuit features on developmental function. The examples include subcircuits encoding positive feedback, mutual repression, and coherent feedforward, as well as signaling interaction circuitry. Within the hierarchy of the endomesoderm GRN, these subcircuits are organized in an intertwined and overlapping manner. Thus, we begin to see how regulatory information encoded at individual nodes is integrated at all levels of network organization to control developmental process.