Journal
DEVELOPMENTAL DYNAMICS
Volume 245, Issue 10, Pages 1029-1042Publisher
WILEY
DOI: 10.1002/DVDY.24435
Keywords
valve; extracellular matrix; fibromodulin; lumican; development; myotendinous junction; cardiac; SLRP; collagen
Categories
Funding
- National Institutes of Health [RO1 HL121382]
- National Institutes of Health-National Institute of General Medical Sciences [P30 GM103342]
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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. (C) 2016 Wiley Periodicals, Inc.
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