Palate morphogenesis. IV. Effects of serotonin and its antagonists on rotation in embryo culture.

Previous studies have localized non-muscle contractile systems in the posterior (region 2) and the anterior (region 3) ends of mouse palates at the time of shelf movement. In order to determine whether these contractile systems function in shelf rotation, effects of pharmacologic agents have been analyzed in embryo culture. First, it was shown that the posterior end of the palate rotates before the anterior end, and its rotation in culture was proportionally greater as development of the embryo progressed. Generally, the posterior end of the palate was more easily inhibited in embryo culture than the anterior end. Serotonin at 10(-8) M to 10(-5) M was shown to significantly stimulate rotation at the anterior end of the palate after 2 h in embryo culture. The effect on the posterior palate was less pronounced. To investigate further the role of this neurotransmitter on palate shelf rotation, serotonin antagonists were employed. Methysergide (10(-4) M) inhibited anterior shelf rotation to 12% of control values (P less than 0.005), while not significantly affecting the posterior end. Ergotamine (10(-6) M) significantly inhibited the stimulation induced by 10(-5) M serotonin (P less than 0.025). Cyproheptadine (10(-9) M) partially inhibited anterior and posterior shelf rotation in embryo culture. When injected into the pregnant dam, cyproheptadine partially inhibited shelf rotation and fusion. The palate was examined histologically after embryo culture. In the presence of 10(-4) M methysergide, the elongated contractile cells in region 3 at the anterior and midpalatal mesenchyme were prevented from rounding. Thus, serotonin may be regulating rotation of the anterior end of the palate by an effect on cell-mediated process.