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

Authors: 
Korotkova DD, Lyubetsky VA, Ivanova AS, Rubanov LI, Seliverstov AV, Zverkov OA, Martynova NY, Nesterenko AM, Tereshina MB, Peshkin L, Zaraisky AG
Citation: 
Cell Rep. 2019 Oct 22;29(4):1027-1040.e6. doi: 10.1016/j.celrep.2019.09.038
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.
Organism or Cell Type: 
Xenopus laevis
Delivery Method: 
microinjection