Regulation of murine embryonic epithelial cell differentiation by transforming growth factors beta.

The expression of some members of the transforming growth factor beta (TGF beta) family of genes in embryonic craniofacial tissue suggests a functional role for these molecules in orofacial development. In an attempt to ascertain a role for the TGF beta s during palatal ontogeny, murine palatal shelves were excised on gestation day (GD) 12, prior to overt epithelial differentiation, grown in organ culture under serum-free conditions and exposed to TGF beta 1 and TGF beta 2 for 18 or 42 h. Shelves were labeled with [3H]-thymidine (20 microCi/ml) during the last 4 h in culture, fixed, dehydrated, embedded in paraffin and sections stained and examined by autoradiography. Treatment of GD12 palates with TGF beta 1 and TGF beta 2 resulted in precocious cessation of medial edge epithelium (MEE) DNA synthesis followed by elimination of the MEE. In addition, this response appeared to be dose-related with higher concentrations of growth factor eliciting a more marked biological response. TGF beta treatment of homologous shelves grown in apposition also resulted in precocious fusion of apposing MEE. Thus, members of the TGF beta family, known to be synthesized by palatal MEE, appear to act in an autocrine/paracrine fashion in this tissue and are capable of regulating differentiation of embryonic palatal medial edge epithelium.