ZFIN ID: ZDB-PUB-171206-5
Shp2-MAPK signalling drives proliferation during zebrafish embryo caudal fin-fold regeneration
Hale, A.J., den Hertog, J.
Date: 2017
Source: Molecular and cellular biology   38(4): e00515-17 (Journal)
Registered Authors: den Hertog, Jeroen
Keywords: MAPK signaling, Shp2, protein-tyrosine phosphatase, regeneration, zebrafish
MeSH Terms:
  • Animal Fins/embryology*
  • Animal Fins/injuries
  • Animal Fins/metabolism
  • Animals
  • Cell Proliferation/physiology
  • Mitogen-Activated Protein Kinases/metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism*
  • Regeneration/physiology
  • Signal Transduction
  • Wound Healing/physiology
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 29203641 Full text @ Mol. Cell. Biol.
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ABSTRACT
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 indicated that Shp2a has a functional signaling 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 similar extents. Expression of mmp9 and junbb, indicative of formation of the wound epidermis and distal blastema, respectively, suggested that 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-mitogen-activated protein kinase (MAPK) signaling in promoting cell proliferation during zebrafish embryo caudal fin fold regeneration.
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