TRANSFORMING GROWTH FACTOR-BETA-3 REGULATES TRANSDIFFERENTIATION OF MEDIAL EDGE EPITHELIUM DURING PALATAL FUSION AND ASSOCIATED DEGRADATIONOF THE BASEMENT-MEMBRANE

Studies on transforming growth factor beta 3 (TGF-beta 3) deficient mi ce have shown that TGF-beta 3 plays a critical role in palatogenesis. These null mutant mice have clefting of the secondary palate, caused b y a defect in the process of fusion of the palatal shelves, A critical step in mammalian palatal fusion is removal of the medial edge epithe lial cells from the midline seam and formation of continuous mesenchym e, To determine in more detail the role of TGF-beta 3 in palatogenesis , we cultured TGF-beta 3 null mutant and wild-type control palatal she lves in an organ culture system. The fate of the medial edge epithelia l cells was studied in vitro using vital cell labeling and immunohisto chemical techniques. Despite clear adherence, the null mutant palatal shelves did not fuse in vitro, but instead the medial edge epithelial cells survived at the midline position, and the basement membrane was resistant towards degradation. Supplementation of the culture medium w ith the mature form of TGF-beta 3 was able to fully correct the defect ive fusion in the null mutant specimens. Our results demonstrate that the reason for the defective palatal fusion in TGF-beta 3 (-/-) sample s is not impaired adhesion. Our data define a specific role for TGF-be ta 3 in the events that control transdifferentiation of the medial edg e epithelial cells including degradation of the underlying basement me mbrane.