title: Molecular profiling of synovial joints: use of microarray analysis to identify factors that direct the development of the knee and elbow.
abstract: BACKGROUND
  Synovial joints develop from the interzone, a dense layer of mesenchymal progenitor cells that marks the site of the future joint. During the morphogenic events that follow, joints attain their distinct shape and organization. The molecular mechanisms controlling the initial specification of synovial joints has been studied, but the question of how individual joints attain the specific structure required for their unique functions remains largely unresolved. Here, we use microarray analysis to compare knee and elbow formation to identify factors involved in the development of specific joints.
  
  
  RESULTS
  The knee is enriched for the hindlimb patterning genes Hoxc9, Hoxc10, and Tbx4 and for Tgfbi, Rspo2, and Sfrp2, factors involved in transforming growth factor-beta/bone morphogenetic protein (TGFβ/BMP) and Wnt signaling. Consistent with these findings, we show that TGFβ signaling directs knee morphogenesis, and is necessary for meniscus development. The tissue surrounding the elbow is highly enriched for genes involved in muscle specification and differentiation, and in splotch-delayed muscleless mutants, elbow, but not knee morphogenesis is disrupted.
  
  
  CONCLUSIONS
  Our results suggest there are fundamental differences in how individual joints develop after interzone formation. Our microarray analyses provides a new resource for further investigation of the pathways involved in the morphogenesis of specific synovial joints.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA. dorothy_pazin@hsdm.harvard.edu
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Pazin
authors.forename: Laura W
authors.initials: LW
authors.lastname: Gamer
authors.forename: Karen A
authors.initials: KA
authors.lastname: Cox
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
mesh_terms: D000818:Animals; D005260:Female; D005552:Forelimb / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007719:Knee Joint / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D011247:Pregnancy; D016212:Transforming Growth Factor beta
chemical_list: D016212:Transforming Growth Factor beta