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-betas 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 [H-3]-thymidine (20-mu-Ci/ml) during the last 4 h in culture, fixed, dehydrated, embedded in parafrin and sections stained and examined by autoradiography. Treatment of GD12 palates with TGF-beta-1 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.