By cutting out one gene, researchers remove a tadpole’s ability to regenerate

Tadpoles of frogs that can typically regrow amputated tails or limbs lost their ability to regenerate after researchers blocked the expression of a newly identified gene that is one of the drivers for this regrowth. Furthermore, scientists hypothesize that the loss of appendage regeneration in warm-blooded animals might have been caused by the gain or loss of this gene, dubbed c-Answer, in an ancestor’s genome during evolution. The work appears October 22 in the journal

Cell Reports

.

“We suppose that genes can only disappear if removing them has advantages for the animal,” says first author Daria Korotkova of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry in Moscow. “So, we suggest that when this gene disappeared from warm-blooded species it was by a mutation, acting as a trade-off for the loss of appendage regeneration.”

Using a computer algorithm, the researchers identified several genes that disappeared in the genomes of warm-blooded vertebrates, including humans, but are present in cold-blooded ones. They did this by searching the DNA of African clawed frogs,

Xenopus laevis

, to determine which genes code for regeneration. They then looked for similar DNA patterns in warm-blooded species, such as chicks, and noted anywhere a gene differed. They then selected one of the identified cold-blooded specific genes, encoding for previously unknown transmembrane protein, and named it c-Answer (cold-blooded animals specific wound epithelium receptor-like).

The research team, including Korotkova, Andrey Zaraisky, Vassily Lyubetsky, Anastasiya Ivanova, Lev Rubanov, Alexander Seliverstov, Oleg Zverkov, Natalia Martynova, Alexey Nesterenko, Maria Tereshina, and Leonid Peshkin, then overexpressed or blocked c-Answer in tadpole embryos. They discovered that enhancing c-Answer allowed tadpoles to regenerate lost tails earlier in their life than those that hatched naturally, whereas tadpoles with c-Answer blocked could transition into frogs but could not regenerate amputated appendages.

“C-Answer modulates at least two important molecular pathways that are common to all vertebrates,” says senior author Zaraisky, head of the laboratory of molecular bases of embryogenesis at the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry. “Its loss in evolution might alter the functioning of these pathways and, accordingly, lead to major physiological transformations.”

“We also found that over expression of c-Answer causes advanced brain growth and larger eyes, which surprised us, since it means c-Answer modulates for regeneration and brain development,” says Korotkova. “However, it was observed that when c-Answer is blocked,

Xenopus laevis

tadpoles had smaller brains, so there is still work to be done in order to better understand this relationship.”

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This work was supported by This work was supported by the Russian Foundation for Basic Research and the National Institutes of Health.

Cell Reports

, Korotkova et al.: “Bioinformatics screening of genes specific for well-regenerating vertebrates reveals a novel regulator of brain development and regeneration: c-answer”

https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31226-4

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