TY - JOUR
T1 - Shp2-MAPK signalling drives proliferation during zebrafish embryo caudal fin-fold regeneration
AU - Hale, Alexander James
AU - den Hertog, Jeroen
N1 - Copyright © 2017 Hale and den Hertog.
PY - 2017/12/4
Y1 - 2017/12/4
N2 - Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a-/-ptpn11b-/- zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin-folds. Rescue experiments indicate that Shp2a has a functional signalling role, requiring its catalytic activity and SH2 domains, but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin-fold regeneration to a similar extent. Expression of mmp9 and junbb, indicative of formation of the wound epidermis and distal blastema, respectively, suggested these processes occurred in ptpn11a-/-ptpn11b-/- zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a-MAPK signalling in promoting cell proliferation during zebrafish embryo caudal fin-fold regeneration.
AB - Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a-/-ptpn11b-/- zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin-folds. Rescue experiments indicate that Shp2a has a functional signalling role, requiring its catalytic activity and SH2 domains, but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin-fold regeneration to a similar extent. Expression of mmp9 and junbb, indicative of formation of the wound epidermis and distal blastema, respectively, suggested these processes occurred in ptpn11a-/-ptpn11b-/- zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a-MAPK signalling in promoting cell proliferation during zebrafish embryo caudal fin-fold regeneration.
KW - Journal Article
U2 - 10.1128/MCB.00515-17
DO - 10.1128/MCB.00515-17
M3 - Article
C2 - 29203641
SN - 0270-7306
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
ER -