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ECB-ART-49315
Curr Top Dev Biol 2021 Jan 01;141:39-73. doi: 10.1016/bs.ctdb.2020.11.004.
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Modularity and hierarchy in biological systems: Using gene regulatory networks to understand evolutionary change.

Hatleberg WL , Hinman VF .


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Modularity and hierarchy are important theoretical concepts in biology, and both are useful frameworks to understand the evolution of complex systems. Gene regulatory networks (GRNs) provide a powerful mechanistic model for modularity in animal development, as they are made up of modular (or self-contained) circuits, which are deployed in a hierarchical manner over time. Over the years, studies in the sea urchin, Strongylocentrotus purpuratus, have provided an illustrative example of how these regulatory circuits are responsible for processes such as cell differentiation and cell state specificity. However, GRNs are themselves made up of a nested series of interactions, as each gene can be regulated by multiple cis-regulatory elements, which can be further broken down into distinct transcription factor binding sites (TFBS). As a result, modularity can be applied to each "level" of this complex hierarchy. Throughout the literature, there is considerable discussion about the roles modular circuits, modular enhancers, and modular TFBS play in evolution, yet there is little discussion about how these nested interactions operate as a whole. In this chapter, we discuss how modular changes at different levels of the GRN hierarchy affect animal development and aim to provide a unified framework to understand the role of modularity in evolution.

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