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Journal of Cell Science 115, 753-760 (2002)
© 2002 The Company of Biologists Limited

Research Article

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

Fang-Xu Jiang1,*, Edouard G. Stanley2, L. Jorge Gonez1 and Leonard C. Harrison1,*

1 Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, PO The Royal Melbourne Hospital, Parkville 3050, Australia
2 Cancer Division, The Walter and Eliza Hall Institute of Medical Research, PO The Royal Melbourne Hospital, Parkville 3050, Australia

Author for correspondence (e-mail: harrison{at}wehi.edu.au )

Accepted 1 November 2001

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 ß1 (TGF-ß1) 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-ß superfamily regulate pancreas epithelial cell development and can promote the formation of islet-like structures in vitro.

Key words: Bone morphogenetic proteins, Pancreas, Epithelial colony, Fetus, Development, ß-cells




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© The Company of Biologists Ltd 2002