PHILADELPHIA – Ants have proven themselves to be the newest (and brightest) animal model on the laboratory block. Nevertheless, "ants-as-animal-model" darlings is a fairly new thing. But not for Shelley Berger, PhD, and Roberto Bonasio, PhD, from the Perelman School of Medicine at the University of Pennsylvania. For the last decade, Berger, Bonasio, and colleagues from the NYU School of Medicine and Arizona State University (ASU), have been working with several ant species (and other animal models) to tease out the molecular inner workings of aging, cancer, and brain neuroscience, among other areas. The Berger and Bonasio labs look at changes in DNA itself as well as changes in how DNA is expressed (the field of epigenetics) to accomplish these discoveries. Berger is the Daniel S. Och University Professor in the department of Cell and Developmental Biology. Bonasio is an assistant professor of Cell and Developmental Biology.
"Social insects such as ants are outstanding models to study how gene regulation affects behavior," Bonasio said. "This is because they live in colonies comprised of individuals with the same genomes but vastly different sets of behaviors." The colony typically includes one queen, carrying out all the egg-laying, and numerous workers, who sacrifice reproduction to provide all other tasks for the group.
This week, in a pair of papers published in Cell, the team turned to an ant species — the Indian jumping ant (Harpegnathos saltator) — that does not behave like most ants. In this species any female worker can change into a "pseudo-queen," in the absence of the true queen and establish dominance on her colony. Berger and colleagues genetically engineered this species in different ways using now-famous CRISPR technology that dramatically changed their social and reproductive behavior.
"In the broadest sense, these studies suggest, albeit indirectly, that the human brain might also be subject to this type of molding," Berger said. "Better understanding, biochemically speaking, how behavior is shaped could reveal insights into disorders in which changes in social communication are a hallmark, such as schizophrenia or depression."
In one study, a CRISPR-engineered mutation in the orco gene disabled the ants' sense of smell. Mutant ants displayed asocial behavior, such as not interacting with other ants in the colony, not foraging for food, and not displaying pre-mating grooming. In these orco mutants, there is stunting of projections made by odor receptors on neurons in ant antennae into the smell center of the ant brain. Ants exhibit cooperative social behaviors that depend on chemical odors called pheromones. The orco gene encodes the co-receptor of all odor receptors and mutations in orco significantly impact ants' sense of smell, and therefore social communication.
In the other study, Bonasio and colleagues injected the brain chemical corazonin into ants transitioning to become a pseudo-queen, which suppressed expression of a brain protein called vitellogenin. This change stimulated worker-like hunting behaviors, while inhibiting pseudo-queen behaviors, such as dueling and egg deposition.
Further, when the team analyzed proteins the ant brain makes during the transition to becoming a pseudo-queen, they found that corazonin is similar to a reproductive hormone in vertebrates. More importantly, they also discovered that release of corazonin gets turned off as workers became pseudo-queens. Corazonin is also preferentially expressed in workers and foragers from other social insect species. In addition to corazonin, several other genes were expressed in a worker-specific or queen-specific way.
Now that ant mutants are a reality, Berger, Bonasio, and their collaborators are primed to make important discoveries on how these and other genes control social behavior in ants and other animals.
In addition to Berger, the senior authors of the ant mutant study are Danny Reinberg at NYU School of Medicine, Claude Desplan at NYU, and Jürgen Liebig at ASU. The study on the behavioral effects of corazonin was performed largely by Janko Gospocic, a postdoctoral fellow in the Bonasio laboratory, with contributions by Emily Shields, a doctoral student in Genomics and Computational Biology and Karl Glastad, a postdoctoral fellow in the Berger laboratory, as well as Reinberg, Liebig, and Tim Linksvayer from Penn. Berger is also director of the Penn Epigenetics Institute.
The ant epigenetic project was funded by a Howard Hughes Medical Institute Collaborative Initiative Award (HCIA #2009005). Ant research in the Bonasio lab is funded by the National Institutes of Health (DP2MH107055), the Searle Scholars Program (15-SSP-102), the Charles E. Kaufman Foundation (KA2016-85223), and a Linda Pechenik Montague Investigator Award.
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