Autism analysis makes the leap to frogs | Spectrum
Earlier this year, researchers reported striking similarities in the functions of 10 autism genes: they all affect brain size and increase the number of immature neurons in the brain. The work raised hopes of finding common biological pathways to autism.
Most of the studies of gene function are done in mice, but that work involved a tiny tropical frog, Xenopus tropicalis, native to West Africa.
These frogs exhibit a number of properties that make them useful for autism research. Any adult can lay thousands of eggs, which will develop into tadpoles in just a week. After the fertilized egg cell has divided, each daughter cell and all of its offspring remain on their respective side. This results in a perfectly halved animal that can only harbor a mutation on one side of its body. Researchers can then observe at an early stage how these cells develop: The first stages of development of the tadpole take place outside the mother’s body. In addition, Xenopus can be made to lay eggs at any time simply by exposing the frog to hormones.
The team edited each of the top 10 autism genes in just one of the two original daughter cells in thousands of Xenopus eggs. As the tadpoles’ brains developed, their two sides developed differently: the inserted mutations resulted in an atypically large or small cerebrum and an unusually large number of immature neurons, all of which were clearly visible to the researchers. “This [tadpole] travels alone and swims, ”says study researcher Helen Willsey, a postdoctoral fellow in the Matthew State laboratory at the University of California, San Francisco. “We can look into the living brain and observe the entire brain development in one dish.”
Thanks to this transparency, research on frogs has led to fundamental discoveries about the brain and nervous system, including the first neurotransmitters and techniques for making human pluripotent stem cells. “Xenopus has made it possible for us to observe the development of the nervous system in an extraordinary way,” said Hazel Sive, dean of the College of Science at Northeastern University in Boston, Massachusetts.
Researchers continue to develop clever methods to study autism and neurological development in amphibians. A research team used frogs to show that deletions in chromosomal region 3q29, which has been linked to autism, can accelerate the process of cell death and identified a possible mechanism for the effects of the deletion. In an unpublished study, another team found that switching off the autism-linked gene CHD7 in Xenopus laevis embryos disrupted the tadpole’s head structure by reducing the expression of a collagen-producing gene. And in a new piece of work, Willsey’s group used frogs to show how certain genetic variants can contribute to both autism and congenital heart disease.
Willsey plans to work with Xenopus tropicalis to link the various biological steps from autism genes to autism traits. “The transition from genes to biology, circuits, and behavior is a huge leap,” says Willsey. “The nice thing about frogs is that you can do all of these things in one system.”
Quote this article: https://doi.org/10.53053/WRUR5688
