FGF-8 in the ventral pharynx alters development of myocardial calcium transients after neural crest ablation

Cardiac neural crest ablation results in depressed myocardial calcium trans ients and elevated proliferation in myocardium at a stage when cardiac neur al crest cells are not in contact with the myocardium. To test the hypothes is that cardiac neural crest-derived cells, which migrate into the caudal, ventral pharynx at stage 14, block a signal from the ventral pharynx, we cu ltured stage 12 chick heart tube or myocardial strips in the presence or ab sence of ventral pharynx. We found that myocardium cultured with ventral ph arynx that had not yet contacted neural crest cells had significantly reduc ed calcium transients and an increased rate of proliferation. Ventral. phar ynx from intact embryos at a stage when neural crest-derived cells had reac hed the pharynx had no effect on myocardial calcium transients. Ventral pha rynx from neural crest-ablated embryos continued to suppress myocardial cal cium transients at this later stage. Myocardium cultured with FGF-2 also sh owed a significant reduction in calcium transients. An FGF-2- neutralizing Ab reversed the deleterious effect of the ventral pharynx on myocardial cal cium transients and proliferation. We therefore examined the expression of FGF-2 and similar FGFs in the ventral pharynx. Only FGF-8 was expressed in a temporospatial pattern that made it a viable candidate for altering the m yocardial calcium transient during stages 14-18. In explant cultures, neutr alizing Ab for FGF-8 rescued development of the myocardial calcium transien t in neural crest-ablated chick embryos.