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. 2020 May 6;6:12. doi: 10.1038/s41540-020-0131-2

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Schematic diagrams demonstrate gradual evolution of network topology of the Notch-1/β-catenin axis in prosimians, simians, Hominoidae and Homininae. Note that sophistication of the topology parallels enhances signalling activity of the Wnt/β-catenin in higher primates. b Schematic diagrams (top) demonstrate gradual evolution of the network topology by recruitment of additional network motifs^76,77 into the existing circuitry of Notch-1/β-catenin axis. Evolution of the microRNA radically alters⁷⁸ the existing genetic network. Evolution of miRNA-4673 in Homininae generates a type-4 coherent feed-forward loop (C4-FFL) that amplifies activity of the Wnt/β-catenin (bottom). Simultaneously, inclusion of Notch-1 in a type-1 incoherent feed-forward loop (I1-FFL) formed by the miRNA reduces the signalling activity of the notch signalling pathway (bottom).