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XB-ART-56396
Cell Rep January 1, 2019; 29 (4): 1027-1040.e6.

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

Korotkova DD , Lyubetsky VA , Ivanova AS , Rubanov LI , Seliverstov AV , Zverkov OA , Martynova NY , Nesterenko AM , Tereshina MB , Peshkin L , Zaraisky AG .


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.

PubMed ID: 31644900
PMC ID: PMC6871517
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ag1 en1 fgf20 fgf8 fgfr1 fgfr2 fgfr3 fgfr4 foxg1 foxo1 hesx1 mbp msx1 myc npl odc1 p2ry1 pax6 piezo1 pnhd ptma ras-dva1 ras-dva2 rax rpe sfrpx six3 trim25 wnt5a
Antibodies: FLAG Ab4 Myc Ab15
Morpholinos: c-answer MO1 foxo1 MO5 sfrpx MO1


Article Images: [+] show captions
References [+] :
Aboitiz, Co-option of signaling mechanisms from neural induction to telencephalic patterning. 2007, Pubmed