TGF-β1 Inhibits Growth and Branching Morphogenesis In Embryonic Mouse Submandibular and Sublingual Glands in Vitro: (Salivary glands/extracellular matrix/epithelium/mesenchyme/organ culture).

Members of the TGF-β superfamily of polypeptides are key regulators in developmental processes. Several studies have shown that expression of TGF-β mRNA and protein are developmentally regulated and that both are prominently expressed in tissues undergoing epithelial-mesenchymal interactions such as branching morphogenesis. It has been shown that TGF-β1 protein is present in E 14 mouse submandibular glands at a time when branching is already establihsed. Here we demonstrate by RT-PCR and immunofluorescence that both TGF-β1 mRNA and protein are present in E 13 submandibular and sublingual glands at a time when branching is being initiated. Addition of TGF-β1 to E 13 rudiments resulted in reductions in organ size and inhibition of branching. Sensitivity to TGF-β1 depended on the developmental stage of the rudiments (early or late E 13) and the dose of growth factor used. TGF-β1 Also caused epithelial abnormalities, notably treated organs had elongated ducts. The effects were most pronounced in the sublingual gland. Taken together these results suggest a regulatory role for endogenous TGF-β1 in the growth and morphogenesis of mouse salivary glands.