PUBLICATION

Wnt signalling controls the response to mechanical loading during Zebrafish joint development

Authors
Brunt, L.H., Begg, K., Kague, E., Cross, S., Hammond, C.L.
ID
ZDB-PUB-170708-7
Date
2017
Source
Development (Cambridge, England)   144(15): 2798-2809 (Journal)
Registered Authors
Brunt, Lucy, Hammond, Chrissy
Keywords
Cartilage, Joint, Mechanics, Morphogenesis, Wnt, Zebrafish
MeSH Terms
  • Animals
  • Cell Movement/genetics
  • Cell Movement/physiology
  • Cell Proliferation/genetics
  • Cell Proliferation/physiology
  • Chondrogenesis/genetics
  • Chondrogenesis/physiology
  • Finite Element Analysis
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology
  • Jaw/embryology
  • Jaw/metabolism
  • Joints/embryology
  • Joints/metabolism*
  • Morphogenesis/genetics
  • Morphogenesis/physiology
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
28684625 Full text @ Development
Abstract
Joint morphogenesis requires mechanical activity during development. Loss of mechanical strain causes abnormal joint development, which can impact long-term joint health. Although cell orientation and proliferation are known to shape the joint, dynamic imaging of developing joints in vivo has not been possible in other species. Using genetic labelling techniques in zebrafish we were able, for the first time, to dynamically track cell behaviours in intact moving joints. We identify that proliferation and migration, which contribute to joint morphogenesis, are mechanically controlled and are significantly reduced in immobilised larvae. By comparison with strain maps of the developing skeleton, we identify canonical Wnt signalling as a candidate for transducing mechanical forces into joint cell behaviours. We show that, in the jaw, Wnt signalling is reduced specifically in regions of high strain in response to loss of muscle activity. By pharmacological manipulation of canonical Wnt signalling, we demonstrate that Wnt acts downstream of mechanical activity and is required for joint patterning and chondrocyte maturation. Wnt16, which is also downstream of muscle activity, controls proliferation and migration, but plays no role in chondrocyte intercalation.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping