A highly regenerative salamander could lead to new regenerative medicine therapies

With its amazing ability to regenerate tissues and organs, its ability to reproduce in a laboratory environment, and the ease with which its genes can be manipulated, the Mexican salamander, or axolotl, holds tremendous promise as a model for the study of regenerative medicine.

But unlike research on traditional models like the mouse, the fruit fly (Drosophila melanogaster) and ascaris (Caenorhabditis elegans), who progressed in genetic age, the study of the axolotl (mexican ambystoma) has been held back by a lack of scientific tools to work with, including sophisticated genomic resources as well as experimental and genetic tools.

That is changing due to research being conducted at the MDI Biological Laboratory in Bar Harbor, Maine, and elsewhere. The development of new tools for working with the axolotl elevates it to the level of established research models and positions the community of scientists who use it as a model of exponential growth. As a result of these changes, the lab is set to become a global epicenter of axolotl research.

The institution’s growing prominence in the axolotl community is due to Prayag Murawala, Ph.D., who joined the faculty last year. Murawala, who previously worked in the lab of Elly Tanaka, Ph.D., the world’s leading axolotl researcher, at the Molecular Pathology Research Institute in Vienna, Austria, brought the latest tools to work with the axolotl, most of which he developed, in his new position, as well as a commitment to fostering the growth of the axolotl as a research model.

Many of the tools that have been developed for working with the axolotl, as well as those that are essential for expanding the scope of axolotl research, were recently described by Murawala in two articles, “The Use of Transgenics in the Laboratory Axolotl” and “Nomenclature of Genes and Transgenics for the Axolotl Laboratory — Ambystoma Mexicanum,“both published in the June 2022 edition of Development dynamic.

In addition to Murawala, authors include Ji-Feng Fei of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China, and, on the nomenclature article, Tanaka and S. Randal Voss, Ph.D., director of the Ambystoma Genetic Stock Center (AGSC) at the University of Kentucky College of Medicine in Lexington, a federally funded center for the distribution of axolotl research animals.

“The ability of some animals to regenerate themselves has fascinated observers for thousands of years, including early MDI Biological Laboratory researchers such as scientific luminaries Thomas Hunt Morgan and Richard J. Goss,” said Hermann Haller, MD, President. “In its efforts to develop the axolotl as a model, Prayag continues a long and venerable laboratory tradition of looking to nature to better understand human health.”

The axolotl, a Mexican salamander that is now nearly extinct in the wild, is a champion of regeneration, with the ability to regenerate almost any part of the body, including the brain, heart, jaws, limbs , lungs, ovaries, spinal cord, skin, tail and more. A better understanding of the cellular and genetic mechanisms underlying this ability could lead to new treatments for traumatic injuries, diseases, birth defects and aging.

Most axolotl research now focuses on the question of fibrosis (scar formation) – or why axolotls regenerate limbs and tails while mammals such as mice and humans form a scar at the site. of an injury. But due to its incredible regenerative abilities, the possibilities for axolotl research are wide open, especially given the plethora of new tools that are becoming available to work with it.

“With these tools in place, we expect exponential growth,” Murawala said. “We only have to look at other animal models to get an idea of ​​the variety of topics that can be studied. Most axolotl research now focuses on limb or tail regeneration, but it is also possible to study regeneration in the brain, heart, lung, spinal cord and more. We have no shortage of biological questions to study.”

The need for transgenic animals

While the axolotl has been studied in vertebrate developmental biology for more than 150 years (most laboratory models are descendants of animals brought to Paris from Mexico in 1863), it has he has received renewed attention in recent years as a model in regenerative biology and medicine thanks to advances in the development of new genetic and genomic resources.

These include transgenic animals, or animals that have been genetically modified for traits important for research. Using gene-editing techniques, researchers can, for example, create animals whose cells are tagged with fluorescent markers, allowing them to study cell behavior under a fluorescent microscope; or animals in which genes have been “knocked out”, allowing them to study gene function.

Currently, few transgenic axolotls are available to US and Canadian researchers at the AGSC – indeed, the lack of transgenic animals is one of the barriers to axolotl research cited in Murawala’s recent transgenic paper. . But that is changing because of his establishment of mechanisms for importing transgenic animals into the United States from Tanaka’s labs and other European labs.

Thanks to these efforts, the already large axolotl colony of non-transgenic animals at the MDI Biological Laboratory is now the largest repository of transgenic axolotls in North America, with 30-40 lineages available to North American researchers. Going forward, Murawala plans to coordinate with the AGSC the distribution of propagated transgenic research animals to the MDI Biological Laboratory.

In addition to advancing research, the distribution of transgenic animals, which can take years to develop, also protects lines that are now only available in a few laboratories from the loss of potential pathogens or other disasters. .

The need for a uniform nomenclature

Besides transgenic animals, another need cited by Murawala is that of a uniform gene and transgenic nomenclature, which is the subject of the second article. Although the large and complex genome of the axolotl, which is 10 times the size of the human genome, has been sequenced by teams from the laboratories of Tanaka and Voss, much work remains to be done to establish the nomenclature of genes and transgenics.

“If we want to exchange information, we must have precise and unambiguous communication, which is why standardized guidelines must be offered,” Murawala said. “If I call a gene one thing and you call it another, it will create confusion. Since the authors of our paper have been heavily involved in the development of axolotl gene constructs and transgenic animals , we were in a good position to write the guidelines.”

Another critical need is for an online database similar to the FlyBase and WormBase databases used in the study of fruit flies and roundworms. Such a database would integrate the genetic, genomic, and biological data essential for effective communication and sharing of findings within the axolotl community and among those studying other salamander models with which axolotls share characteristics.

In collaboration with laboratory scientists James Godwin, Ph.D., who also studies the axolotl, and Joel H. Graber, Ph.D., director of the Computational Biology and Bioinformatics Core, and in coordination with researchers from ‘axolotl around the world, Murawala is developing an “AxoBase” database that aims to unify axolotl-related resources on a single website. The group plans to launch a basic website in the next few months, although developing a full database will take much longer.

About Hector Hedgepeth

Check Also

Experts explain the ‘perfect storm’ of endemic RSV and influenza

The headlines of the past few weeks are sounding the alarm about earlier and more …