PUBLICATION

Iroquois Proteins Promote Skeletal Joint Formation by Maintaining Chondrocytes in an Immature State

Authors
Askary, A., Mork, L., Paul, S., He, X., Izuhara, A.K., Gopalakrishnan, S., Ichida, J.K., McMahon, A.P., Dabizljevic, S., Dale, R., Mariani, F.V., Crump, J.G.
ID
ZDB-PUB-151112-6
Date
2015
Source
Developmental Cell   35: 358-65 (Journal)
Registered Authors
Crump, Gage DeKoeyer, Dale, Rodney M., He, Xinjun, McMahon, Andrew
Keywords
none
MeSH Terms
  • Animals
  • Bone and Bones/metabolism*
  • Cartilage, Articular/metabolism*
  • Cartilage, Articular/pathology
  • Cell Differentiation/physiology*
  • Chondrocytes/metabolism*
  • Transcription Factors/metabolism*
  • Zebrafish/metabolism*
PubMed
26555055 Full text @ Dev. Cell
Abstract
An early event in skeletal joint development is the specification of articular chondrocytes at the joint surface. Articular chondrocytes are distinct in producing lower levels of cartilage matrix and not being replaced by bone, yet how they acquire these properties remains poorly understood. Here, we show that two members of the Iroquois transcriptional repressor family, Irx7 and Irx5a, function to block chondrocyte maturation at the developing hyoid joint of zebrafish. These Irx factors suppress the production of cartilage matrix at the joint in part by preventing the activation of a col2a1a enhancer by Sox9a. Further, both zebrafish Irx7 and mouse IRX1 are able to repress cartilage matrix production in a murine chondrogenic cell line. Iroquois proteins may therefore have a conserved role in keeping chondrocytes in an immature state, with the lower levels of cartilage matrix produced by these immature cells contributing to joint flexibility.
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