Bone morphogenetic proteins promote development of fetal pancreas epithelial colonies containing insulin-positive cells.

Extracellular signals that guide pancreas cell development are not well characterized. In an in vitro culture system of dissociated pancreas cells from the E15.5 mouse fetus we show that, in the presence of the extracellular matrix protein laminin-1, bone morphogenetic proteins (BMPs-4, -5 and -6) promote the development of cystic epithelial colonies. Transforming growth factor beta1 (TGF-beta1) and activin A antagonise this effect of BMP-6 and inhibit colony formation. Histological analysis revealed that the colonies are composed of E-cadherin-positive epithelial cells, which in localised areas are insulin positive. The colonies also contain occasional glucagon-positive cells, but no somatostatin- or alpha-amylase-positive cells. These findings indicate that members of the TGF-beta superfamily regulate pancreas epithelial cell development and can promote the formation of islet-like structures in vitro.