Axolotls, or aquatic salamanders, have the unique ability of begin able to regenerate any limb as well as parts of their brains. Scientists at ETH Zurich’s Treutlein Lab and the Tanaka Lab at the Institute of Molecular Pathology in Vienna decided to dive deeper and see if they are able to regenerate all the different cell types in their brain, including the connections linking one brain region to another.
The team focused in on the telencephalon of the axolotl, which in humans, is the largest division of the brain containing a region called the neocortex. This region plays a key role in animal behavior and cognition. They used scRNA-seq to identify the different types of cells that make up the axolotl’s telencephalon, including different types of neurons as well as progenitor cells (cells that can divide into more of themselves or turn into other cell types). When axolotl regeneration was put to the test by removing one section of their telencephalon and applying a specialized method of scRNA-seq, the team captured and sequenced all the new cells at different stages of regeneration, from 1-12 weeks after injury. Three main phases of brain regeneration was observed: rapid increase in progenitor cells, differentiating process begins, and neuroblasts separating into the same types of neurons that were originally lost. Ultimately, we found that all cell types that were removed had been completely restored.Thankfully, we already have self-assembling gel that has been injected into paralyzed mice to help them walk again.
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We used trajectory inference to construct differentiation trajectories of homeostatic neurogenesis and found that ependymoglia largely progress through distinct intermediate neuroblast types and use specific gene regulatory networks to form distinct glutamatergic neuron types. We tracked cycling cells upon injury of the telencephalon and found an injury-specific ependymoglia transcriptional state characterized by up-regulation of wound healing and cell migration genes at the beginning of regenerative neurogenesis,” said the researchers.
