INHIBITION OF TGF-BETA(3) (BUT NOT TGF-BETA(1) OR TGF-BETA(2)) ACTIVITY PREVENTS NORMAL MOUSE EMBRYONIC PALATE FUSION

The critical stage of palatal development is the fusion of apposing in dividual palatal shelves. Palatal shelves, from the day 13 murine embr yo, cultured in vitro fuse normally in the absence of exogenous factor s. Therefore, some endogenous factor(s) is responsible for the normal fusion process, Prevention of mature TGF-beta(3), activity during a sp ecific time window of development in palate organ cultures, either by antisense oligodeoxynucleotides or neutralizing antibody, resulted in failure of palate fusion, Northern analysis was used to demonstrate th at the antisense treatment down-regulated TGF-beta(3) mRNA, Inhibition of TGF-beta(1) or -beta(2), activity (by either antibodies or antisen se oligodeoxynucleotides) had no such effect on palate development and palate fusion was normal. These data indicate an isoform specific rol e for TGF-beta(3), in palatal fusion.