Fig. 4. Evolution of gene regulatory networks during early bilaterian evolution. Colored boxes are transcriptional domains where the state of the domain is dependent upon the presence of the product of the gene of the same color. Stage 1. Initial pattern, similar to that in a Type 1 embryonic system (developmental process in which embryonic lineages proceed directly to expression of differentiation genes) (Davidson, 1991; Davidson, 2001). (A) The genes in the box to left transduce spatial embryonic cues (thick green arrow) and activate an initial gene (green), which in turn activates two additional genes (red and orange) all of which produce transcription factors; the orange gene also cross-regulates the red gene. These transcription factors in turn regulate the gene battery to right. This gene battery encodes proteins used for a differentiated cell type (a-d); each gene has at least two cis-regulatory inputs, indicated in orange and red with ‘x’ denoting other inputs which may vary from gene to gene. (B) Stage 2. Later evolutionary stage: the cell differentiation battery shown in Stage 1 has now been incorporated into a pattern formation system that controls an evolutionarily new morphogenetic process deriving from the state in Stage 1. The additional boxes (Stage 2 and Stage 3) represent new multicellular spatial transcription domains. Only the red gene from Stage 1 is shown in this figure; the red gene is still activated at its initial embryonic address via the green gene as in the ancestor of Stage 1. A new regulatory linkage has appeared, so that the transcriptional activator from the red gene now controls the purple gene, generating the purple transcriptional domain. A growth circuit has also been added. A second cis-regulatory module has been added to the red gene, allowing it to be activated by the purple gene product or repressed by a signal (S) from the underlying spatial domain (Stage 3). The result at Stage 4 is to mount the differentiation gene battery on morphological structure of which the patterning and growth are dependent on the yellow and purple transcriptional domains. Redrawn with permission from Fig. 5.7 of Davidson (Davidson, 2001).