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

Cell Differentiation/physiology*
Zebrafish/metabolism*
Animals
Cartilage, Articular/metabolism*
Cartilage, Articular/pathology
Bone and Bones/metabolism*
Transcription Factors/metabolism*
Chondrocytes/metabolism*

(all 8)

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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
acana	irx7^el538/el538	standard conditions	Protruding-mouth	pharyngeal arch 2 skeleton joint	ISH	Fig. 3
acana	irx7^el538/el538	standard conditions	Long-pec	pharyngeal arch 2 skeleton joint	ISH	Fig. 3
acana	WT	standard conditions	Protruding-mouth	pharyngeal arch 2 skeleton chondrocyte	ISH	Fig. 3
acana	WT	standard conditions	Long-pec	pharyngeal arch 2 skeleton chondrocyte	ISH	Fig. 3
col2a1a	irx7^el538/el538	standard conditions	Protruding-mouth	pharyngeal arch 2 skeleton joint	ISH	Fig. 3
col2a1a	irx7^el538/el538	standard conditions	Long-pec	pharyngeal arch 2 skeleton joint	ISH	Fig. 3
col2a1a	WT	standard conditions	Long-pec	pharyngeal arch 2 skeleton chondrocyte	ISH	Fig. 3
col2a1a	WT	standard conditions	Protruding-mouth	pharyngeal arch 2 skeleton chondrocyte	ISH	Fig. 3
dlx2a	WT	standard conditions	Prim-25	pharyngeal arch 1 mesenchymal cell	ISH	Fig. 1
dlx2a	WT	standard conditions	Prim-25	pharyngeal arch 2 mesenchymal cell	ISH	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
Df(Chr01:hand2)s6/s6	standard conditions	Long-pec	pharyngeal arch 2 joint irx5a expression increased distribution, abnormal	Fig. 1
Df(Chr01:hand2)s6/s6	standard conditions	Long-pec	pharyngeal arch 2 joint irx7 expression increased distribution, abnormal	Fig. 1
edn1^{tf216b/tf216b}	standard conditions	Long-pec	pharyngeal arch 2 joint irx5a expression absent, abnormal	Fig. 1
edn1^{tf216b/tf216b}	standard conditions	Long-pec	pharyngeal arch 2 joint irx7 expression absent, abnormal	Fig. 1
el49Tg; kca4Tg	heat shock	Long-pec	pharyngeal arch 2 joint irx5a expression absent, abnormal	Fig. 1
el49Tg; kca4Tg	heat shock	Long-pec	pharyngeal arch 2 joint irx7 expression absent, abnormal	Fig. 1
irx5a^el574/el574; irx7^el538/el538	standard conditions	Protruding-mouth	ceratohyal-interhyal joint chondrocyte development increased process quality, abnormal	Fig. 3
irx5a^el574/el574; irx7^el538/el538	standard conditions	Protruding-mouth	interhyal-hyosymplectic joint chondrocyte development increased process quality, abnormal	Fig. 3
irx5a^el574/el574; irx7^el538/el538	standard conditions	Protruding-mouth	pharyngeal arch 2 skeleton embryonic skeletal joint development decreased process quality, abnormal	Fig. 3
irx5a^el574/el574; irx7^el538/el538	standard conditions	Protruding-mouth	pharyngeal arch 2 skeleton joint ab1-col2a labeling increased amount, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b719		Small Deletion	kat6a
el10Tg	Tg(sox10:DsRed)	Transgenic Insertion
el49Tg	Tg(UAS:bmp4,myl7:EGFP)	Transgenic Insertion
el361Tg	Tg(sox10:mCherry-CAAX)	Transgenic Insertion
el375Tg	Tg(sox10:EGFP-CAAX)	Transgenic Insertion
el377Tg	Tg(UAS:KikGR,cryaa:Cerulean)	Transgenic Insertion
el483Tg	TgBAC(col2a1a:EGFP)	Transgenic Insertion
el538		Indel	irx7
el540		Small Deletion	irx7
el559Tg	TgBAC(col2a1a:mCherry-NTR)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
irx5a	TALEN1-irx5a	TALEN
irx7	TALEN1-irx7	TALEN

Fish

Fish
Df(Chr01:hand2)s6/s6
edn1^{tf216b/tf216b}
el10Tg; el483Tg
el10Tg; nu13Tg
el49Tg; kca4Tg
el375Tg
irx5a^el574/el574
irx5a^el574/el574; irx7^el538/el538
irx5a^el576/el576
irx7^el538/el538

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-col2a	monoclonal		IgG1	Mouse
Ab1-smad	polyclonal	smad1 smad5 smad9	IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
Cerulean	EFG	Cerulean
DsRed	EFG	DsRed
EGFP	EFG	EGFP
GAL4	EFG	GAL4
KikGR	EFG	KikGR
mCherry	EFG	mCherry
NTR	EFG	NTR

Mapping

Askary et al., 2015 ZDB-PUB-151112-6 PMID:26555055

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

Askary et al., 2015

ZDB-PUB-151112-6
PMID:26555055