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Published June 6, 2017 | Published + Supplemental Material
Journal Article Open

Assessing regulatory information in developmental gene regulatory networks


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.

Additional Information

© 2017 National Academy of Sciences. Edited by Douglas H. Erwin, Smithsonian National Museum of Natural History, Washington, DC, and accepted by Editorial Board Member Neil H. Shubin January 24, 2017 (received for review August 17, 2016). We thank Deanna Thomas for her help in the preparation of the figures. This work was supported by National Institutes of Health Grant HD 037105. Author contributions: I.S.P. and E.H.D. designed research; I.S.P. and E.H.D. performed research; and I.S.P. wrote the paper. The authors declare no conflict of interest. This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, "Gene Regulatory Networks and Network Models in Development and Evolution," held April 12–14, 2016, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Gene_Regulatory_Networks. This article is a PNAS Direct Submission. D.H.E. is a guest editor invited by the Editorial Board. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1610616114/-/DCSupplemental.

Attached Files

Published - PNAS-2017-Peter-5862-9.pdf

Supplemental Material - pnas.1610616114.sapp.pdf


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