title: Iroquois Proteins Promote Skeletal Joint Formation by Maintaining Chondrocytes in an Immature State.
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.
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Amjad
authors.initials: A
authors.lastname: Askary
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Mork
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Paul
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Xinjun
authors.initials: X
authors.lastname: He
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Audrey K
authors.initials: AK
authors.lastname: Izuhara
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Suhasni
authors.initials: S
authors.lastname: Gopalakrishnan
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Ichida
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.affiliation: Department of Biology, Loyola University Chicago, Chicago, IL 60660, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Dabizljevic
authors.affiliation: Department of Biology, Loyola University Chicago, Chicago, IL 60660, USA.
authors.forename: Rodney
authors.initials: R
authors.lastname: Dale
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Francesca V
authors.initials: FV
authors.lastname: Mariani
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: gcrump@usc.edu.
authors.forename: J Gage
authors.initials: JG
authors.lastname: Crump
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D014157:Transcription Factors