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

Abstract

Summary: 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. : Poor regeneration in warm-blooded animals could be caused by gene loss in evolution. Here, we describe a bioinformatic approach to identify lost genes. One of these, c-answer, regulates regeneration and brain development in cold-blooded animals. Thus, loss of c-answer could promote evolutionary changes related to regeneration and brain development in warm-blooded animals. Keywords: bioinformatics screening, genes extinction, forebrain, regeneration, genome evolution, FGF signaling, purinergic signaling