Bisdiamine inhibits extracellular matrix formation and cell proliferation of atrioventricular mesenchyme from developing chick heart valves

Abnormalities of the cushion tissues lead to atrioventricular septal defect s (AVSD) and truncus arteriosus (TA). Bisdiamine exposure in the embryo fre quently causes AVSD and TA in the newborn chick, mouse, or rat. We studied the effects of bisdiamine an mesenchymal cells grown in aggregate culture i solated from the developing atrioventricular valves of the stage-36 chick e mbryo. Fibronectin extracellular matrix formation and cell proliferation in the aggregates were assessed in various media. Chick serum stimulated the cells to produce an extracellular matrix and to divide, and the inclusion o f bisdiamine inhibited both responses. if we isolated an extracellular matr ix from a monolayer of mesenchymal cells and added the sonicated matrix to the medium containing serum and bisdiamine, the matrix incorporated into th e aggregates and the cells entered the mitotic cycle. Our previous work est ablished that cells need to attach to an intact extracellular matrix to beg in cell division. Thus, we suggest that bisdiamine inhibits the normal form ation of the extracellular matrix, leading to reduced cell proliferation, b ut it does not affect matrix-cell interaction. The lack of cushion growth i n situ may be the cause of AVSD or TA. (C) 1999 Wiley-Liss, Inc.