Expression of type VI collagen in the developing mouse heart.
During development, the embryonic atrioventricular (AV) endocardial cushions undergo a morphogenic process to form mature valve leaflets and the membranous septa in the heart. Several extracellular matrix (ECM) proteins are expressed in the developing AV endocardial cushions, but it remains to be established if any specific ECM proteins are necessary for normal cushion morphogenesis. Abnormal development of the cardiac AV valves is a frequent cause of congenital heart defects, particularly in infants with trisomy 21 (Down syndrome). The genes encoding the alpha1 and alpha2 chains of type VI collagen are located on human chromosome 21 within the region thought to be critical for congenital heart defects in trisomy 21 infants. This suggests that the type VI collagen alpha1(VI) and alpha2(VI) chains may be important in normal AV valve morphogenesis. As a first step in understanding the role of type VI collagen in valve development, the authors examined the normal spatial and temporal expression patterns of mRNA and protein for type VI collagen in the embryonic mouse heart. Ribonuclease protection assay analysis demonstrates cardiac expression of the type VI collagen for alpha1(VI), alpha2(VI), and alpha3(VI) transcripts beginning at embryonic days 11-11.5 of mouse development. In situ hybridization studies demonstrate a coordinated pattern of cardiac expression within the AV valves for each type VI collagen chain from embryonic day 11.5 through the neonatal period. Immunohistochemical studies confirm a concentrated type VI collagen localization pattern in the endocardial cushions from the earliest stages of valve development through the neonatal period. These data indicate that type VI collagen is expressed in the developing AV canal in a pattern consistent with cushion tissue mesenchymal cell migration and proliferation, and suggest that type VI collagen plays a role in the morphogenesis of the developing cardiac AV endocardial cushions into the valve leaflets and membranous septa of the heart.
Klewer
S E
SE
Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA. sklewer@peds.arizona.edu
Krob
S L
SL
Kolker
S J
SJ
Kitten
G T
GT
D000818:Animals; D002642:Chick Embryo; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000737:chemistry; D005318:Fetal Heart / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D009024:Morphogenesis; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
D012333:RNA, Messenger; D003094:Collagen