To understand the deep evolutionary questions around development of specific organs, scientists often create chimeras, where one organism contains cells from multiple genomes. For the first time, scientists have created a chimeric brain between two different species, rats and mice. While similar, rats and mice started evolving away from each other over 12 million years ago, twice as long as for humans and chimpanzees, our closest relatives. To create chimeras from such evolutionarily different species, two research groups injected rat stem cells into a developing mouse embryo, resulting in functioning rat-mouse brains.

The first research group created a chimera focused on the largest region of the brain, the forebrain. In just the mouse cells, they deactivated a gene important for forebrain development, such that the entire forebrain was primarily from the rat cells. Even though rat brains grow to be about 4 times the size of mouse brains, these rat cells surprisingly developed at about the same pace as the rest of the mouse. This suggests that the mouse environment altered the rat cells so that their growth course would match the mouse. The second research group created rat-mouse chimeras then examined their neural circuitry. They took a special interest in the olfactory system, which is the part of our nervous system that controls our sense of smell. Amazingly, when the mice olfactory neurons were destroyed, the rat olfactory neurons kicked in, and the mice gained a partially restored sense of smell.

Developing such complex understandings of how neurons of different species can coexist together could not have come from prior techniques, which involved things like transplanting grown tissue into an adult mouse brain. The methods in these two studies present an exciting new way to understand how brain development is affected by the activity within each cell versus the environment. These techniques can also be expanded to other species and in the future, can drive research into using transplants grown in other species to help irreversible brain damage.

The first study was led by Jia Huang, Bingbing He, and Liejie Li, all researchers at the University of Texas Southwestern Medical Center, and Xiali Yang, Xin Long, and Yinghui Wei, all researchers at the Chinese Academy of Sciences.

The second study was led by Benjamin Throesch, a researcher at the University of California, San Diego, and Muhammad Khadeesh bin Imtiaz, a researcher at the University of Texas Southwestern Medical center.

Corresponding Author: Alex Yenkin

Press Article: Rat Neurons Repair Mouse Brains That Lack a Sense of Smell (Scientific American)

Original Articles: Generation of rat forebrain tissues in mice (Cell)

Functional sensory circuits built from neurons from two species (Cell)

Image Credit: NIH

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