Abnormal interactions of embryonic mouse trisomy 16 heart fibroblasts with extracellular matrix components in vitro.
Trisomy 16 mice have cardiovascular abnormalities thought to arise from altered development and maturation of the cardiac cushions. Cell-cell and cell-extracellular matrix (ECM) interactions play critical roles in heart morphogenesis. To begin to examine the potential involvement of cell-ECM interactions in abnormal trisomy 16 heart development, fibroblasts were isolated from normal and trisomy 16 embryonic mouse hearts. Behavior of these cells was compared in bioassays involving cell-ECM interactions including cell attachment and collagen gel contraction. Significant differences in cell-ECM interactions were found between fibroblasts isolated from normal and trisomy 16 embryonic hearts. Trisomy 16 cells attached poorly to collagen and laminin compared to normal fibroblasts. Trisomy 16 heart fibroblasts also contracted collagen gels less effectively than normal heart fibroblasts. Cell-ECM interactions are largely mediated by ECM receptors of the integrin family. Expression of beta 1 integrins was examined at the mRNA and protein levels in normal and trisomy 16 fibroblasts. Analyses of integrin expression indicated the pattern of integrins produced by normal and trisomy 16 fibroblasts to be similar. These results indicate that fibroblasts isolated from embryonic trisomy 16 mouse hearts interact with several ECM components including collagen and laminin less efficiently than fibroblasts from normal mouse embryos. As cell-ECM interactions play significant roles in cardiac cushion development, abnormal interactions may contribute to defective atrioventricular septal morphogenesis in the trisomy 16 mouse.
Carver
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Department of Developmental Biology and Anatomy, University of South Carolina School of Medicine, Columbia 29208, USA. carver@dcsmserver.sc.edu
D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology*; D003094:Collagen / Q000032:analysis; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006343:Heart Septal Defects / Q000196:embryology; D019012:Integrin beta1 / Q000032:analysis; D007797:Laminin / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D014314:Trisomy
D019012:Integrin beta1; D007797:Laminin; D012333:RNA, Messenger; D003094:Collagen