Chapter Summary

This chapter uses embryonic development as an example for mechanisms of gene regulation. Many of the genes studied here were identified as part of forward genetic screens for developmental mutants.

The even-skipped gene is an example of how multiple enhancers can regulate a single gene. There are five classes of genes controlling anterior-posterior patterning in Drosophila: maternal effect, gap, pair-rule, segment polarity, and segment identity. Eve is a pair-rule gene, regulated by maternal effect and gap genes.

Although much of the work in developmental genetics was done in the fruit fly, the lessons learned are applicable to other organisms as well. The mammalian Hox genes are structurally and functionally similar to those seen in Drosophila. The hedgehog ortholog Shh is as well.

Shh plays a role in the development of multiple organ systems, including the nervous system and limb development. This is controlled by multiple enhancers. A mutation in the ZRS enhancer causes anomalies of limb development in humans. Evolutionarily, a 17 base-pair deletion in the snake ZRS enhancer may explain why snakes do not have legs.

Chromatin structure plays an important role in gene regulation in eukaryotes, with enhancers needing to contact promoters in three-dimensional space, even though they can be hundreds of thousands of base pairs from their target sequence.

Other levels of gene expression are also important. miRNAs are small 20 base RNA molecules that influence the stability of RNA transcripts and can block translation of mRNA. Our understanding of miRNA function has led to the development of RNA techniques for reverse genetic screens as well as potential therapeutics to treat diseases like such as cancer and metabolic disorders.