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

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

Author information

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (IBCH RAS), 16/10 Miklukho-Maklaya str., Moscow 117997, Russia.
2
The Institute for Information Transmission Problems, Russian Academy of Sciences (IITP RAS), 19 Bolshoy Karetny str., Moscow 127051, Russia.
3
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (IBCH RAS), 16/10 Miklukho-Maklaya str., Moscow 117997, Russia; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1/40 Leninskie Gory, Moscow 119991, Russia.
4
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
5
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (IBCH RAS), 16/10 Miklukho-Maklaya str., Moscow 117997, Russia. Electronic address: azaraisky@yahoo.com.

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.

KEYWORDS:

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

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