The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
Synovial joints enable smooth articulations between different skeletal elements and are essential for the motility of vertebrates. Despite decades of extensive studies of the molecular and cellular mechanisms of limb and skeletal development, the molecular mechanisms governing synovial joint formation are still poorly understood. In particular, whereas several signaling pathways have been shown to play critical roles in joint maintenance, the mechanism controlling joint initiation is unknown. Here we report that Osr1 and Osr2, the mammalian homologs of the odd-skipped family of zinc finger transcription factors that are required for leg joint formation in Drosophila, are both strongly expressed in the developing synovial joint cells in mice. Whereas Osr1(-/-) mutant mice died at midgestation and Osr2(-/-) mutant mice had only subtle defects in synovial joint development, tissue-specific inactivation of Osr1 in the developing limb mesenchyme in Osr2(-/-) mutant mice caused fusion of multiple joints. We found that Osr1 and Osr2 function is required for maintenance of expression of signaling molecules critical for joint formation, including Gdf5, Wnt4 and Wnt9b. In addition, joint cells in the double mutants failed to upregulate expression of the articular cartilage marker gene Prg4. These data indicate that Osr1 and Osr2 function redundantly to control synovial joint formation.
Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Yang
Y
Gao
Yu
Y
Lan
Han
H
Liu
Rulang
R
Jiang
D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D017746:Joint Capsule / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D038081:Organogenesis / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D016335:Zinc Fingers; D051176:beta Catenin / Q000378:metabolism; D000099158:Proteoglycan 4
D018398:Homeodomain Proteins; D019426:Integrases; D011509:Proteoglycans; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C121641:Osr1 protein, mouse; C438618:Osr2 protein, mouse; C498837:Prg4 protein, mouse; D000099158:Proteoglycan 4; C489936:Prrx1 protein, mouse; C045073:Cre recombinase
Genes Dev. 2004 Oct 1;18(19):2404-17
15371327
Genetics. 1996 Sep;144(1):171-82
8878683
Dev Biol. 2003 Feb 1;254(1):116-30
12606286
Nature. 1994 Apr 14;368(6472):639-43
8145850
EMBO J. 1990 Nov;9(11):3795-804
2120051
Development. 2001 Apr;128(8):1253-64
11262227
Arch Biochem Biophys. 1994 May 15;311(1):144-52
8185311
Genesis. 2007 Oct;45(10):618-24
17941042
J Rheumatol Suppl. 2000 Oct;60:6-8
11032095
Science. 1998 May 29;280(5368):1455-7
9603738
Dev Biol. 1998 Jun 15;198(2):277-85
9659933
Genes Dev. 2005 Mar 15;19(6):709-18
15769943
Birth Defects Res C Embryo Today. 2003 May;69(2):144-55
12955858
J Biol Chem. 1981 Jun 10;256(11):5921-5
7240180
Development. 1999 Mar;126(6):1305-15
10021348
Dev Biol. 2008 Apr 1;316(1):62-73
18295755
EMBO J. 2003 May 15;22(10):2443-52
12743038
Development. 2004 Jul;131(13):3207-16
15175245
Dev Biol. 2005 Dec 15;288(2):582-94
16223478
Cell. 2001 Feb 9;104(3):341-51
11239392
Dev Cell. 2006 Jul;11(1):93-104
16824956
J Embryol Exp Morphol. 1977 Jun;39:115-27
886251
Development. 2003 Dec;130(24):5943-52
14573519
J Rheumatol. 2000 Mar;27(3):594-600
10743795
Dev Biol. 1999 May 1;209(1):11-27
10208739
Genes Dev. 1995 May 15;9(10):1237-49
7758948
Birth Defects Res C Embryo Today. 2005 Sep;75(3):237-48
16187328
Mech Dev. 2001 Sep;107(1-2):175-9
11520675
Genes Dev. 2001 Sep 1;15(17):2307-19
11544187
Dev Dyn. 2008 Sep;237(9):2284-94
18729226
Am J Anat. 1978 Apr;151(4):475-85
645613
Development. 1998 Jan;125(1):21-31
9389660
Genesis. 2002 Jun;33(2):77-80
12112875
Mech Dev. 1995 Mar;50(1):17-28
7605748
Dev Biol. 2002 Mar 1;243(1):44-54
11846476
Development. 2006 Aug;133(15):2995-3004
16790474
J Bone Joint Surg Am. 2001;83-A Suppl 1(Pt 1):S23-30
11263662
Development. 2002 Aug;129(15):3645-56
12117814
Biochem Biophys Res Commun. 1999 Jan 27;254(3):535-41
9920774
Science. 2009 Feb 27;323(5918):1232-4
19251632
Development. 1996 Dec;122(12):3969-79
9012517
Dev Biol. 2003 Nov 15;263(2):282-95
14597202
Mech Dev. 1999 Jun;84(1-2):157-60
10473132
Development. 2006 Aug;133(15):3039-49
16818445
Gene Expr Patterns. 2006 Oct;6(8):826-34
16554187
Development. 2006 Nov;133(21):4145-9
17021046
Dev Dyn. 1999 May;215(1):45-53
10340755
Dev Biol. 2007 May 1;305(1):40-51
17336282
EMBO J. 1996 Jun 17;15(12):3182-96
8670819
Development. 1987 Mar;99(3):383-91
2958266
Dev Biol. 2009 Apr 15;328(2):200-9
19389375