Emerging properties of animal gene regulatory networks

Abstract

Gene regulatory networks (GRNs) provide system level explanations of developmental and physiological functions in the terms of the genomic regulatory code. Depending on their developmental functions, GRNs differ in their degree of hierarchy, and also in the types of modular sub-circuit of which they are composed, although there is a commonly employed sub-circuit repertoire. Mathematical modelling of some types of GRN sub-circuit has deepened biological understanding of the functions they mediate. The structural organization of various kinds of GRN reflects their roles in the life process, and causally illuminates both developmental and evolutionary process.

Figure 1. ‘Birdseye’ views of structural properties of representative developmental GRNs

a–c, Diagrammatic view of sub-circuits and sub-circuit functions in three different GRNs. Each box represents a GRN sub-circuit consisting of a small number of regulatory genes and their functional linkages. Coloured dots and numbers refer to the similarly coded sub-circuit types in Table 1. Red arrows indicate linkages between sub-circuits, that is, regulatory feeds from one sub-circuit to another. a, GRN for skeletogenic mesoderm lineage specification in sea urchin embryos. b, GRN for pancreatic developmental process, leading to β cell specification and insulin gene transcription. c, GRNs typical of terminal binary fate choices in haematopoietic stem cells and other similar situations, as discussed in text.

Figure 2. Structural characteristics of downstream effector gene cassettes and their control functions

a, Typical differentiation gene battery, as discussed elsewhere. Here each effector gene codes for a cell-type-specific protein required to generate the cell-specific output. These effector genes are all transcribed specifically in the given cell type in response to a small number of regulatory factors, which are themselves the output of the controlling specification GRN. Every effector gene of the battery is specifically controlled by these inputs. The immediate drivers of the battery shown cross-regulate (as is often the case). b, Structure that may be typical of morphogenetic effector gene cassettes. Here the output of the specification GRN is used to control transcription of only a minor fraction of key effector genes, and these in some way trigger or nucleate the process. But many of the proteins required for the function are widely expressed.