Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development.
To expand our insight into cardiac development, a comparative DNA microarray analysis was performed using tissues from the atrioventricular junction (AVJ) and ventricular chambers of mouse hearts at embryonic day (ED) 10.5-11.0. This comparison revealed differential expression of approximately 200 genes, including cartilage link protein 1 (Crtl1). Crtl1 stabilizes the interaction between hyaluronan (HA) and versican, two extracellular matrix components essential for cardiac development. Immunohistochemical studies showed that, initially, Crtl1, versican, and HA are co-expressed in the endocardial lining of the heart, and in the endocardially derived mesenchyme of the AVJ and outflow tract (OFT). At later stages, this co-expression becomes restricted to discrete populations of endocardially derived mesenchyme. Histological analysis of the Crtl1-deficient mouse revealed a spectrum of cardiac malformations, including AV septal and myocardial defects, while expression studies showed a significant reduction in versican levels. Subsequent analysis of the hdf mouse, which carries an insertional mutation in the versican gene (CSPG2), demonstrated that haploinsufficient versican mice display septal defects resembling those seen in Crtl1(-/-) embryos, suggesting that reduced versican expression may contribute to a subset of the cardiac abnormalities observed in the Crtl1(-/-) mouse. Combined, these findings establish an important role for Crtl1 in heart development.
Wirrig
Elaine E
EE
Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Snarr
Brian S
BS
Chintalapudi
Mastan R
MR
O'neal
Jessica L
JL
Phelps
Aimee L
AL
Barth
Jeremy L
JL
Fresco
Victor M
VM
Kern
Christine B
CB
Mjaatvedt
Corey H
CH
Toole
Bryan P
BP
Hoffman
Stanley
S
Trusk
Thomas C
TC
Argraves
W Scott
WS
Wessels
Andy
A
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D006820:Hyaluronic Acid / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D053675:Versicans / Q000378:metabolism; D000099249:Proteoglycan Link Protein