Bioinformatics Screening of Genes Specific for Well-Regenerating Vertebrates Reveals c-answer, a Regulator of Brain Development and Regeneration

对再生能力良好的脊椎动物特异基因进行生物信息学筛选,揭示大脑发育和再生的调节因子 c-answer

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作者:Daria D Korotkova, Vassily A Lyubetsky, Anastasia S Ivanova, Lev I Rubanov, Alexander V Seliverstov, Oleg A Zverkov, Natalia Yu Martynova, Alexey M Nesterenko, Maria B Tereshina, Leonid Peshkin, Andrey G Zaraisky

Abstract

The molecular basis of higher regenerative capacity of cold-blooded animals comparing to warm-blooded ones is poorly understood. Although this difference in regenerative capacities is commonly thought to be a result of restructuring of the same regulatory gene network, we hypothesized that it may be due to loss of some genes essential for regeneration. We describe here a bioinformatic method that allowed us to identify such genes. For investigation in depth we selected one of them encoding transmembrane protein, named "c-Answer." Using the Xenopus laevis frog as a model cold-blooded animal, we established that c-Answer regulates regeneration of body appendages and telencephalic development through binding to fibroblast growth factor receptors (FGFRs) and P2ry1 receptors and promoting MAPK/ERK and purinergic signaling. This suggests that elimination of c-answer in warm-blooded animals could lead to decreased activity of at least two signaling pathways, which in turn might contribute to changes in mechanisms regulating regeneration and telencephalic development.

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