Role of BMP signalling in the developing pancreas
The pancreas is an organ of endodermal origin. It is composed of two different tissues; exocrine (acini and ducts) and endocrine (islet of Langerhans). The Bone Morphogenetic Proteins (BMP) are secreted growth factors from the TGFβ superfamily. These proteins are implicated in numerous biological responses in various cell types. A recent study in mice showed the importance of BMP signalling for the normal function of adult β cells. Indeed, an inactivation of this pathway leads to impaired glucose homeostasis and finally to diabetes. The aim of this project was to investigate the role of the BMPs during pancreatic development. We have shown by In situ hybridisation that BMP ligands are expressed in the pancreas and that the BMP signalling pathway is active only in endocrine cells. Briefly, at E10.5 BMP7 is expressed homogeneously in the whole pancreatic epithelium whereas at E14.5 only acinar cells are stained. Reporter mice show that the pathway is active in endocrine cells already at E10.5 and until the end of development. No activity was detected in pancreatic precursors and endocrine progenitors. The fact that the receptors and ligands are present and the pathway is active led us to investigate whether BMPs have a role during pancreatic development. In order to investigate this role, we performed an in vivo loss of function study by knocking out the two BMP specific type I receptors ALK3 and ALK6 in the pancreas. Double knockout embryos presented a normal islet structure and exocrine compartment but showed a 2-fold decrease in the endocrine cell fraction both at E14.5 and E18.5. Further experiments will be needed to know whether ALKs and BMPs affect endocrine cell proliferation, differentiation or death.