PUBLICATION

Shp2-MAPK signalling drives proliferation during zebrafish embryo caudal fin-fold regeneration

Authors

Hale, A.J., den Hertog, J.

ID

ZDB-PUB-171206-5

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
Regeneration/physiology
Zebrafish/embryology*
Zebrafish/metabolism
Cell Proliferation/physiology
Signal Transduction
Wound Healing/physiology
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism*
Animals
Mitogen-Activated Protein Kinases/metabolism

(all 14)

PubMed

29203641 Full text @ Mol. Cell. Biol.

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.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
TL	chemical treatment: EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor	Day 5	fin regeneration decreased efficacy, abnormal	Fig. 6
TL	amputation: caudal fin	Day 4	regenerating fin cell population proliferation decreased occurrence, abnormal	Fig. 6
TL	amputation: caudal fin, chemical treatment: EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor	Day 4	caudal fin regenerating fin ab2-pcna labeling decreased amount, abnormal	Fig. 6
TL	amputation: caudal fin, chemical treatment: EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor	Day 4	regenerating fin cell population proliferation decreased occurrence, abnormal	Fig. 6
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)	control	Day 4	regenerating fin MAPK cascade decreased occurrence, abnormal	Fig. 5
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)	amputation: caudal fin	Day 4	caudal fin regenerating fin ab2-pcna labeling decreased amount, abnormal	Fig. 4
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)	amputation: caudal fin	Day 4	caudal fin regenerating fin ab9-mapk labeling decreased amount, abnormal	Fig. 5
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)	amputation: caudal fin	Day 4	regenerating fin cell population proliferation decreased occurrence, abnormal	Fig. 4
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)	amputation: caudal fin	Day 4	regenerating fin MAPK cascade decreased occurrence, abnormal	Fig. 5
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)	amputation: caudal fin	Day 5	fin regeneration decreased efficacy, abnormal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hu3459		Point Mutation	ptpn11a
hu5920		Point Mutation	ptpn11b

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
ptpn11a^{hu3459/hu3459}; ptpn11b^{hu5920/hu5920} (TL)
ptpn11a^hu3459/+; ptpn11b^{hu5920/hu5920} (TL)
ptpn11b^{hu5920/hu5920} (TL)
TL

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab2-pcna	monoclonal	pcna	IgG2a	Mouse
Ab9-mapk	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Mapping

Hale et al., 2017 ZDB-PUB-171206-5 PMID:29203641

Shp2-MAPK signalling drives proliferation during zebrafish embryo caudal fin-fold regeneration

Hale et al., 2017

ZDB-PUB-171206-5
PMID:29203641