Aquatic Salamanders with Brain Regeneration Abilities Reveal Brain Evolution Secrets

Brain cell regrowth requires complex responses over time and brain region. Identifying the cell types involved in this process can help biologists learn more about brain regrowth and provide potential targets for regenerative medicine research. However, progress in this field has been slow due to the mammalian brain’s limited regrowth capacity and incomplete knowledge of the regrowth process at the cellular and molecular levels. Salamander brains share some structures with mammalian brains, but not all. They can also regenerate more quickly in response to damage.

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Axolotl. Credit: David Stang

Axolotls, a type of salamander, can regrow damaged and multiple organs, including the brain. As a result, axolotls could serve as a model for studying neuronal regrowth. Biologists were curious as to why this species can regrow all neuronal cell types and the synapses that connect one brain region to another. The scientists developed a picture of the cells that make up a portion of the axolotl brain, showing its regeneration and evolution across species.

RNA sequencing method shows the process of axolotl brain regrowth

A technique known as single-cell RNA sequencing (scRNA-seq) can help researchers determine cell-gene expression. Biologists can use this method to count the number of active genes in each cell. The sequencing method presents a picture of the cell activities.

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Study scientists used the RNA method to identify the various cell types that comprise the axolotl telencephalon, including neurons and progenitor cells. They discovered that many progenitor cells go through an intermediate cell phase called neuroblasts before developing to mature neurons, previously unknown in axolotls.

They then tested axolotl regrowth by removing a portion of their brain. The biologists pictured and sequenced all of the new cells at various stages of regrowth. They discovered that the cells regenerated after removal.

The researchers discovered that the species’ brain regrowth occurs in three distinct stages. The first stage begins with a rise in progenitor cells, and a small percentage of these cells initiate wound healing. Progenitor cells start to divide into neuroblasts in the second phase. Finally, the neuroblasts divide into the same neuron types lost during the first phase. The continual regrowth of the cells helps in axolotl brain regrowth.

Clinical significance

Identifying all the axolotl brain cell types can also help pave the way for innovative regenerative medicine studies. The ability of mouse and human brains to repair or regenerate themselves is low. Presently, medical interventions for severe brain injury focus on drugs, rehabilitation, and stem cell therapies to enhance or promote repair. Examining the genes and cell types that allow axolotls to regrow neurons nearly perfectly may be vital to improving treatments for severe injuries and unlocking human regrowth potential. These findings can be beneficial in treating brain injuries.

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Different cell forms serve unique purposes. These cells carry varying genes and can specialize in biological roles. The current study creates an understanding of the regrowth process in the aquatic salamander. The findings also enable biologists to understand evolutionary and biological trends across species.


Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration



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