BIOCHEMICAL AND GENETIC BASIS OF PALATAL SHELF FUSION IN MICE: H-2, CAMP-MEDIATED VERSOS H-2, CORTICOSTEROID MEDIATED EFFECTS

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On a biochemical level, both steroids and CAMP are known to play a role in palate formation. CAMP levels rise prior to fusion, inducing epithelial cell death and adhesiveness. Steroid injections increase the incidence of palatal clefting; the magnitude of the effect is strain dependent, and strains which are less susceptible have been shown to have fewer steroid receptors. On a genetic level, susceptibility to steroid-induced cleft palate is H-2 linked. Basal CAMP levels in some tissues also appear to be H-2 determined. The mechanism by which steroids induce cleft palate is unknown, but CAMP may be involved. Premature cell death and/or glycocalyx formation as a result of abnormally high levels of CAMP might well prevent subsequent growth and fusion of shelves. H-2 might mediate its effect through control of basal or steroid-induced cAMP levels, through both, or neither. To determine the relationship between steroids, cAMP, palatal fusion, and H-2, we have been measuring the developmental curve of palatal shelf cAMP levels in congenic lines differing in both H-2 and cleft palate susceptibility, with and without steroid injections. To date, no difference in basal palatal shelf CAMP levels have been found. Steroid induced levels are significantly higher, but strain differences are not yet apparent. The results do not indicate whether steroids are exerting a permissive effect on cAMP levels or whether the more usual, transcriptional control mechanism is at work.