Like Bicoid, most of the segmentation genes encode transcription regulator proteins. Their control by the egg-polarity genes and their actions on one another and on still other genes can be deciphered by comparing gene expression in normal and mutant embryos. By using appropriate probes to detect RNA transcripts or their protein products, one can observe genes switch on and off in changing patterns. By comparing these patterns in different mutants, one can begin to discern the logic of the entire gene control system.
The products of the egg-polarity genes provide the global positional signals in the early embryo (see Figure 21–17). The Bicoid protein, as we have seen, acts as 0.2 mm
Figure 21–19 Examples of the phenotypes of mutations affecting egg-polarity genes and the three types of segmentation genes. In each case, the areas shaded in green on the normal larva (left) are deleted in the mutant or are replaced by mirror-image duplicates of the unaffected regions. (Modified from c. Nüsslein-Volhard and e. Wieschaus, Nature 287:795–801, 1980. With permission from Macmillan publishers Ltd.) a morphogen and activates different sets of genes at different positions along the A-P axis: some gap genes are only activated in regions with high levels of Bicoid, others only where levels of Bicoid are lower. After the gap gene products refine their positions by mutual repression, they provide a second tier of positional signals that act more locally to regulate finer details of patterning. Gap genes act by controlling the expression of yet other genes, including the pair-rule genes. The pair-rule genes, in turn, collaborate with one another and with the gap genes to set up a regular, periodic pattern of expression of the segment-polarity genes, which collaborate with one another to define the internal pattern of each individual segment (Figure 21–20).
The initial steps in creation of the segmental pattern occur before cellularization of the syncytial blastoderm and are governed by the combinatorial effects of transcription regulators, as discussed in detail in Chapter 7 for the regulation of the expression of the pair-rule gene Even-skipped (see pp. 394–396). After cellularization, the segment-polarity genes further subdivide each segment into smaller domains. A large subset of the segment-polarity genes codes for components of two signaling pathways—the Wnt pathway and the Hedgehog pathway, including the secreted signal proteins Wingless (the first-named member of the Wnt family) and Hedgehog. (The Hedgehog pathway was first discovered through study of Drosophila segmentation, and it takes its name from the prickly appearance of the surface of the Hedgehog mutant embryo.) Wingless and Hedgehog are synthesized in different bands of cells that serve as signaling centers within each segment. The two proteins mutually maintain each other’s expression, while regulating the expression of genes such as Engrailed in neighboring cells (Figure 21–21). In such a manner, a series of sequential inductions creates a fine-grained pattern of gene expression within each segment.
egg-polarity, Gap, and pair-rule Genes create a transient pattern that Is remembered by Segment-polarity and Hox Genes
The gap genes and pair-rule genes are activated within the first few hours after fertilization. Their mRNA products initially appear in patterns that only approximate the final picture; then, within a short time, this fuzzy initial pattern resolves itself into a regular, crisply defined system of stripes. But this pattern itself is unstable and transient: as the embryo proceeds through gastrulation and beyond, the pattern disintegrates. The genes’ actions, however, have passed on an enduring memory of their patterns of expression by inducing the expression of certain segment polarity genes along with Hox genes (discussed shortly). After a period of pattern refinement mediated by cell–cell interactions, the expression patterns of these new groups of patterning genes is stabilized to provide positional labels that serve to maintain the segmental organization of the larva and adult fly.