The advent of Drosophila melanogaster (fruit fly) as a model organism has transformed modern biology in the 20th century. A brief history of how Drosophila opened new ways of seeing genes and helped understand the construction and the functioning of organisms can be found in this short article by Alfonso Martinez Arias entitled “Drosophila melanogaster and the Development of Biology in the 20th Century“.
More to the point of our first paper, the experiments that earned Nüsslein-Volhard and Wieschaus their Nobel prize aimed to identify genes involved in the development of Drosophila melanogaster embryos. At this point (the late 1970s and early 1980s) little was known about the genetic and molecular mechanisms by which multicellular organisms develop from single cells to morphologically complex forms during embryogenesis.
Fruit flies have long been an important model organism in genetics due to their small size and quick generation time, which makes even large numbers of them relatively easy to maintain and observe in the laboratory. Nüsslein-Volhard and Wieschaus identified genes involved in embryonic development by a series of genetic screens. They generated random mutations in fruit flies using a chemical. Some of these mutations affected genes involved in the development of the embryo. Nüsslein-Volhard and Weischaus took advantage of the segmentedform of Drosophila larvae to address the logic of the genes controlling development. In normal unmutated Drosophila, each segment produces bristles called denticles in a band arranged on the side of the segment closer to the head (the anterior). The researchers looked at the pattern of segments and denticles in each mutant under the microscope, and were therefore able to work out that particular genes were involved in different processes during development based on their differing mutant phenotypes (such as fewer segments, gaps in the normal segment pattern, and alterations in the patterns of denticles on the segments). Many of these genes were given descriptive names based on the appearance of the mutant larvae, such as hedgehog, gurken (German: “cucumbers”), and Krüppel ( “cripple”). Later, researchers identified exactly which gene had been affected by each mutation, thereby identifying a set of genes crucial for Drosophila embryogenesis. The subsequent study of these mutants and their interactions led to important new insights into early Drosophiladevelopment, especially the mechanisms that underlie the step-wise development of body segments.
These experiments are not only distinguished by their sheer scale (with the methods available at the time, they involved an enormous workload), but more importantly by their significance for organisms other than fruit flies. It was later found that many of the genes identified here had homologues in other species. In particular, the homeobox genes (coding for transcription factors critically involved in early body development) are found in all metazoans, and usually have similar roles in body segmentation.
These findings have also led to important realizations about evolution – for example, that protostomes and deuterostomes are likely to have had a relatively well-developed common ancestor with a much more complex body plan than had been conventionally thought. Additionally, they greatly increased our understanding of the regulation of transcription, as well as cell fate during development.
Here is a preparation of the cuticle from a Drosophila embryo, similar to those examined by Nüsslein-Volhard. Note the bands of denticles on the left hand side (towards the head) of each segment:
Source: Wikipedia
