The axolotl, also known as the Ambystoma mexicanum, is an aquatic salamander that can regenerate its spine, heart and limbs. New neurons can be made throughout the life of these salamanders. Even if a large part of the brain is removed, adult axolotls can still regenerate parts of their brain. Axolotl brain regeneration has a limited ability to rebuild original tissue.
How can axolotl's regenerate their brain after an injury?
As a researcher studying regeneration at the cellular level (opens in new tab), I and my colleagues wondered if they had found the answer. In our recently published study, we created an atlas of the cells that make up a part of the axolotl brain, which shed light on both the way it regenerates and brain evolution.
Different cells have different functions. Different genes allow them to specialize in certain roles. Understanding what types of cells are in the brain can help clarify how the brain works. Researchers can try to find biological trends across species by using it.
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One way to understand which cells are expressing which genes is to use a technique called single-cellRNA-seq. Researchers can use this tool to count the genes in a sample. A snapshot of the activities each cell was doing when it was collected is provided by this.
This tool has made it possible to understand the types of cells in the brain of animals. In fish, reptiles, mice, and humans, scientists have used scRNA-seq. The missing piece of the puzzle is the brain.
The telencephalon was the focus of our team. The telencephalon is the largest part of the brain and contains a region called the neocortex, which plays a key role in animal behavior. The neocortex has grown in size more than any other brain region. The telencephalon has a variety of cells that have grown in complexity over time, making this region an intriguing area to study.
We identified the different types of cells that make up the axolotl telencephalon using scRNA-seq. When progenitor cells become neurons, we identified what genes are active and found that many pass through an intermediate cell type called neuroblasts.
We removed a section of their telencephalon to test axolotl regeneration. We were able to sequence all the new cells at different stages of regeneration using a specialized method. All cell types that were removed had been restored.
Brain regeneration takes place in three main phases. The first phase begins with a rapid increase in the number of progenitor cells, and a small fraction of these cells start to heal wounds. progenitor cells begin to differentiate The same types of neurons that were lost in phase one are regained in phase three.
We discovered that the severed connections between the removed area and other areas of the brain had been restored. The regenerated area regained its original function after being re-wired.
Adding to the evolutionary puzzle allows researchers to understand how the brain and cells have changed over time.
When we compared our axolotl data with other species, we found that cells in their telencephalon show similarities to the hippocampus, the region of the brain involved in memory formation. There are some similarities between axolotl cell types and the neocortex, the area of the brain known for perception, thought and spatial reasoning in humans. The areas of the brain that are similar are evolutionarily conserved or stayed the same over the course of evolution.
Our study sheds light on the process of brain regeneration, but we don't know what external signals start it. We don't know if the processes we identified are still available to animals that evolved later in time.
We don't solve the brain evolution puzzle on our own. The Tosches Lab at Columbia University looked at the diversity of cell types in a salamander, while the Fei lab at the Guangdong Academy of Medical Sciences in China looked at the different types of cells.
It is possible to identify all the cell types in the axolotl brain. The brains of humans and mice have lost their ability to repair themselves. Analyzing the genes and cell types that allow axolotls to accomplish nearly perfect regeneration may be the key to improve treatments for severe injuries.
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