title: Development of myotendinous-like junctions that anchor cardiac valves requires fibromodulin and lumican.
abstract: There are many patients that exhibit connective tissue related cardiac malformations but do not have mutations in collagen genes. The Small Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind collagen and regulate fibril assembly in other biological contexts.
  
  
  
  FMOD deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support. Ectopic connective and/or myocardial tissue(s) was associated with the more severe cardiac valve anomalies in FMOD; LUM deficient mice. At postnatal day 0 (P0) there was an increase in the mesenchymal cell number in the regions where valve cusps anchor in FMOD; LUM deficient mice compared to WT. The cardiac valve anomalies correlated with the highest levels of FMOD expression in the heart and also where myotendinous junctions (MTJ) components biglycan, collagen type I alpha 1, and collagen type VI, are also localized.
  
  
  
  The postnatal assembly of the collagen-rich ECM in regions where cardiac valves anchor, that we have designated 'myotendinous-like junctions' (MTLJ) requires the SLRPs FMOD and LUM. Moreover, FMOD and LUM may facilitate mesenchymal cell differentiation in late stages of cardiac valve development. Developmental Dynamics 245:1029-1042, 2016. © 2016 Wiley Periodicals, Inc.
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
authors: Loren E
authors: LE
authors: Dupuis
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
authors: Lorna
authors: L
authors: Doucette
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
authors: A Kittrell
authors: AK
authors: Rice
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
authors: Ashton E
authors: AE
authors: Lancaster
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
authors: Matthew G
authors: MG
authors: Berger
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Shukti
authors: S
authors: Chakravarti
authors: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina. kernc@musc.edu.
authors: Christine B
authors: CB
authors: Kern
mesh_terms: D000818:Animals; D058578:Biglycan / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism; D000071235:Fibromodulin / Q000235:genetics / Q000378:metabolism*; D006351:Heart Valves / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D007150:Immunohistochemistry; D000071234:Lumican / Q000235:genetics / Q000378:metabolism*; D051379:Mice
chemical_list: D058578:Biglycan; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024142:Collagen Type VI; C000604332:Fmod protein, mouse; D000071234:Lumican; D000071235:Fibromodulin
keywords: SLRP; cardiac; collagen; development; extracellular matrix; fibromodulin; lumican; myotendinous junction; valve