Hyperplastic conotruncal endocardial cushions and transposition of great arteries in perlecan-null XXXX .

@entity19 @entity3886 @entity600 @entity597
Perlecan is a heparan- @entity597 proteoglycan abundantly expressed in pericellular matrices and basement membranes during development. Inactivation of the perlecan gene in @entity19 is lethal at two developmental stages: around E10 and around birth. We report a high incidence of @entity600 of the cardiac outflow tract in perlecan-deficient embryos. @entity3886 was diagnosed in 11 out of 15 late embryos studied (73%). Three of these 11 embryos also showed @entity600 . Mesenchymal cells in the outflow tract were abnormally abundant in mutant embryos by E9.5, when the endocardial-mesenchymal transformation starts in wild-type embryos. At E10.5, mutant embryos lacked well-defined spiral endocardial ridges, and the excess of mesenchymal cells obstructed sometimes the outflow tract lumen. Most of this anomalous mesenchyme expressed the smooth muscle cell-specific alpha-actin isoform, a marker of the neural crest in the outflow tract of the @entity19 . In wild-type embryos, perlecan is present in the basal surface of myocardium and endocardium, as well as surrounding presumptive neural crest cells. We suggest that the excess of mesenchyme at the earlier stages of conotruncal development precludes the formation of the spiral ridges and the rotation of the septation complex in order to achieve a concordant ventriculoarterial connection. The observed mesenchymal overpopulation might be due to an uncontrolled migration of neural crest cells, which would arrive prematurely to the heart. Thus, perlecan is involved in the control of the outflow tract mesenchymal population size, underscoring the importance of the extracellular matrix in cardiac morphogenesis.
