Development of myotendinous‐like junctions that anchor cardiac valves requires fibromodulin and lumican. Issue 10 (25th August 2016)

• Record Type: Journal Article
• Authors: Dupuis, Loren E.; Doucette, Lorna; Rice, A. Kittrell; Lancaster, Ashton E.; Berger, Matthew G.; Chakravarti, Shukti; Kern, Christine B.
• Is Part Of: Developmental dynamics. Volume 245:Issue 10(2016)
• Page Start: 1029
• Page End: 1042
• Publication Date: 2016-08-25
• Subjects: valve -- extracellular matrix -- fibromodulin -- lumican -- development -- myotendinous junction -- cardiac -- SLRP -- collagen; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24435
• Languages: English
• ISSNs: 1058-8388

Abstract

Abstract : Background : 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.Results : 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.Conclusions : 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. Key findings: FMOD expression is restricted to ECM regions where cardiac valves anchor. Loss of FMOD and LUM results in cardiac valve anomalies. Ectopic connective and myocardial tissue results from FMOD and LUM deficiency. Fomd in concert with Lum inhibits mesenchymal cell proliferation. Regions where cardiac valves anchor are designated 'Myotendinous‐like Junctions'