By Lucy Huang
Model organisms have deepened our understanding of diverse biological concepts, including animal behavior, environmental changes, molecular genetics, developmental biology, and speciation. What defines a model organism is quite broad. Any organism that is easy to care for, lives short generations, and produces a large number of offspring at one time can potentially be used in research. As research progresses, the scientific community gathers knowledge about which organisms are best-suited for particular types of studies.
As the largest group in the animal kingdom, insects make fantastic study subjects. They are wildly diverse and can be utilized in a variety of fields of study. While these invertebrates may seem far removed from biomedical and genetic research, they have been useful in understanding fundamental biological systems and theories. One of the most significant studies on genetics in the twentieth century involved the use of Drosophila melanogaster. Thomas Hunt Morgan received a Nobel Prize in 1933 “for his discoveries concerning the role played by the chromosome in heredity.” These results have broad applications for research on animal and human biology.
While Morgan was working at Columbia University, he began breeding D. melanogaster by the hundreds. After three years of breeding fruit flies, a white-eyed mutant fly finally appeared in April 1910. The next step, of course, was to breed this white-eyed male mutant fly with its red-eyed, wild-type sisters. The first generation (F1) produced all red-eyed flies, suggesting that the white-eye gene is recessive and the red-eye gene dominant. When Morgan mated the siblings from the F1 generation, the new generation (F2) had three red-eyed flies to every one white-eyed fly — following the 3:1 ratio of Mendelian genetics for recessive traits. When Morgan took a closer look at the white-eyed flies from the F2 generation, he noticed they were all male. Not only was the white-eye gene recessive, it was also linked to sex.
The sex-linked factor was the evidence Morgan needed to cement the concept of gene-based heredity. When Morgan examined the fruit fly chromosomes under the microscope, he noticed a difference between the female and male pairs; the female chromosomes had identical X pairs while the male had an X and Y chromosome. This led him to conclude that the X in a male fly is inherited from his mother and the Y chromosome is inherited from the father. The emergence of this one white-eyed fruit fly allowed Morgan to take Mendel’s abstract concept of inheritance and develop it into the more tangible chromosomal theory of heredity.
Morgan’s initial work on D. melanogaster genetics would later lead to the development of the first genetic map, the discovery of X-ray induced mutagenesis, the discovery of Hox genes, as well as thousands of other important contributions to the scientific world not limited to disease modeling, pharmacological testing, and neurobiology.
Entomological model organisms have even taught us some of the underlying mechanisms that animals use to develop from fertilized eggs to their adult bodies. Tribolium castaneum, the red flour beetle, has been especially useful in understanding how vertebrates determine their body plans during development. T. castaneum development can be easily manipulated with RNA interference (RNAi). By injecting specific double-stranded RNA fragments, gene expression can be inhibited. Unlike traditional knockdown mutations that exist during an organism’s entire life span, RNAi can be administered at different stages of development.
Important research on segmentation has focused heavily on T. castaneum. Susan J. Brown’s group at Kansas State University has been studying one group of genes known as the Wnt genes. These genes help the developing beetle body determine which end is going to be the head and which will be the rear. The expression of the Wnt genes produces a gradient of proteins with the highest concentration in the rear (posterior) end and the lowest concentration at the head (anterior) end.
In 2008, Brown, along with colleagues at Kansas State University and the University of Tuebingen, were able to identify nine Wnt genes in the T. castaneum genome. By using a special technique known as in situ hybridization to tag their transcripts, the group was able to determine when and where the genes were being expressed. When they noticed redundancies in some of the Wnt genes, they were able to use RNAi to identify the three Wnt genes (Wnt1, Wnt8/D and WntA) essential for development during the blastoderm stage. The group also noted that depletion of the genes WntD/8 and Wnt1 in T. castaneum produced similar outcomes to the depletion to the analogues genes in vertebrates.
While the Wnt genes can be found in numerous arthropods and vertebrates, they are expressed during different developmental stages and processes. This makes it difficult to identify a single ancestral and conserved process controlled by this pathway. By studying the Wnt pathway in T. castaneum and other model organisms, scientists can better understand the inner workings of this pathway and follow the evolution of it in more complex organisms.
Developmental biology is closely related to regenerative biology. The way that the body regenerates new tissue is similar to the way that growing embryos develop. In both cases, cells need to divide rapidly to generate new daughter cells. Once there are enough new cells, they stop dividing and differentiate into specific cell types based on their location.
In the last 40 years, D. melanogaster has been used to understand regenerative biology by providing insight on the pathway of stem cells. D. melanogaster use many of the same developmental mechanisms utilized in vertebrate development, making them an ideal organism to study the molecular and genetic pathways of regeneration. Most of what we have learned about the molecular pathway of stem cells, we have learned from studying D. melanogaster. For example, we have discovered that stem cell populations have ways to control division cycles as well as specific signaling pathways to induce differentiation. By observing the stem cell populations in D. melanogastera, we have determined that each population of stem cells responds to different pathways and signals. Studying these stem cell populations in different model organisms will not only be an invaluable resource, it will also provide insight on the evolution of stem cell regulation.
As scientists continue to study insects such as D. melanogaster and T. castaneum, they provide the community with resources and methods for further research, reinforcing them as model organisms.
Lucy Huang is a science writer based in NYC. She has a BA in molecular biology from Skidmore College. Read more of her work at “A Luce Concept of Science.”