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

Cell Rep. 2019 Oct 22;29(4):1027-1040.e6. doi: 10.1016/j.celrep.2019.09.038.


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.

Keywords: FGF signaling; bioinformatics screening; forebrain; genes extinction; genome evolution; purinergic signaling; regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / metabolism*
  • Brain / physiology
  • Computational Biology
  • Gene Expression Regulation, Developmental*
  • MAP Kinase Signaling System
  • Neurogenesis*
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism
  • Receptors, Purinergic P2Y1 / genetics
  • Receptors, Purinergic P2Y1 / metabolism
  • Regeneration*
  • Xenopus laevis


  • Receptors, Fibroblast Growth Factor
  • Receptors, Purinergic P2Y1