Investigating Zebrafish Biochemistry in Search of Mechanisms of Neural Regeneration

Zebrafish are highly regenerative, capable of regrowing organs, and even nervous system tissue such as the retina. Research groups investigate these species in search of specific mechanisms of proficient regeneration, with the hope that they can be ported over to human biochemistry. In the best case scenario, mechanisms of this nature could still exist in mammals, retained in order to conduct embryonic development, but actively suppressed in some way in adults, possibly because such suppression reduces cancer risk. The existing evidence is suggestive that this is the case, and the work here adds further support.

Researchers mapped the genes of animals that have the ability to regenerate retinal neurons. For example, when the retina of a zebrafish is damaged, cells called the Müller glia go through a process known as reprogramming. During reprogramming, the Müller glia cells will change their gene expression to become like progenitor cells, or cells that are used during early development of an organism. Therefore, these now progenitor-like cells can become any cell necessary to fix the damaged retina.

Like zebrafish, people also have Müller glia cells. However, when the human retina is damaged, the Müller glia cells respond with gliosis, a process that does not allow them to reprogram. "After determining the varying animal processes for retina damage recovery, we had to decipher if the process for reprogramming and gliosis were similar. Would the Müller glia follow the same path in regenerating and non-regenerating animals or would the paths be completely different? This was really important, because if we want to be able to use Müller glia cells to regenerate retinal neurons in people, we need to understand if it would be a matter of redirecting the current Müller glia path or if it would require an entirely different process."

The research team found that the regeneration process only requires the organism to "turn back on" its early development processes. Additionally, researchers were able to show that during zebrafish regeneration, Müller glia also go through gliosis, meaning that organisms that are able to regenerate retinal neurons do follow a similar path to animals that cannot. While the network of genes in zebrafish was able to move Müller glia cells from gliosis into the reprogrammed state, the network of genes in a mouse model blocked the Müller glia from reprogramming. From there, researchers were able to modify zebrafish Müller glia cells into a similar state that blocked reprogramming while also having a mouse model regenerate some retinal neurons. Next, the researchers will aim to identify the number of gene regulatory networks responsible for neuronal regeneration and exactly which genes within the network are responsible for regulating regeneration.

Link: https://ibms.nd.edu/news/researchers-identify-process-for-regenerating-neurons-in-the-eye-and-brain/

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