The segment-polarity gene Engrailed provides a good example. Its RNA transcripts form a series of 14 bands in the cellular blastoderm, each approximately one-cell wide. These stripes lie immediately anterior to similar stripes of expression of another segment polarity gene, Wingless. As the cells in the developing embryo continue to grow, divide, and move, a mutually reinforcing signal between the Wingless expressing cells and the Engrailed expressing cells maintains narrow stripes of their expression (see Figure 21–21). After three cell cycles, newly expressed regulators stabilize an Engrailed expression pattern that will last
Figure 21–20 An example of the regulatory hierarchy of egg-polarity, segmentation, and Hox genes. as discussed in the text, there are three groups of segmentation genes. the photographs show mrNa expression patterns of representative examples of genes of each type. (courtesy of Stephen Small.)
Figure 21–21 Mutual maintenance of Hedgehog and Wingless expression.
engrailed is a transcription regulator (blue) that drives the expression of Hedgehog. Hedgehog encodes a secreted protein (red) that activates its signaling pathway in neighboring cells and thereby drives them to express the Wingless gene. In turn, Wingless encodes a secreted protein (green) that acts back on neighbors of the Wingless-expressing cell to maintain their expression of Engrailed and Hedgehog. as indicated, the same control loop repeats along the a-p axis of the fly. (Based on
S. Dinardo et al., Curr. Opin. Genet. Dev. 4:529–534, 1994.) throughout the life of the fly, long after the signals that induced and refined it have disappeared. The segment borders will form at the posterior edge of each such Engrailed stripe (Figure 21–22).
In addition to regulating the segment-polarity genes, the products of pair-rule genes collaborate with those of gap genes to induce the precisely localized activation of a further set of genes—originally called homeotic selector genes and now often called Hox genes, for reasons that will become clear shortly. It is the Hox genes that permanently distinguish one segment from another. In the next section, we examine these important genes in detail and consider their role in cell memory; we shall see that this role is critical in a wide range of animals, including ourselves.
Hox Genes permanently pattern the a-p axis
As animal development proceeds, the body becomes more and more complex. But again and again, in every species and at every level of organization, we find that complex structures are made by repeating a few basic themes, with variations. Thus, a limited number of basic differentiated cell types, such as muscle cells or fibroblasts, recur with subtle individual variations in different sites. These cell types are organized into a limited variety of tissue types, such as muscle or tendon, which again are repeated with subtle variations in different regions of the body. From the various tissues, organs such as teeth or digits are built— molars and incisors, fingers and thumbs and toes—a few basic kinds of structure, repeated with variations.
Wherever we find this phenomenon of modulated repetition, we can break down the developmental biologist’s problem into two kinds of questions: what is the basic construction mechanism common to all the objects of the given class, and how is this mechanism modified to give the observed variations in different animals? The segments of the insect body provide a good example. We have thus far sketched the way in which the rudiment of a single body segment is constructed and how cells within each segment become different from one another. We now consider how one segment becomes determined, or specified, to be different from another.