EmPanMes (333800)

  https://cordis.europa.eu/project/id/333800

  FP7 (2007-2013)

  Cellular composition of the pancreas: elucidating the role of mesenchymal signaling pathways

  Marie-Curie Action: "Career Integration Grants" (FP7-PEOPLE-2012-CIG)

  developmental biology  ·  diabetes  ·  homeostasis  ·  enzymes

  2013-03-01 Start Date (YY-MM-DD)

  2017-02-28 End Date (YY-MM-DD)

  € 100,000 Total Cost

  Description

The pancreas constitutes of various cell types with distinctive function. Exocrine cells produce and secrete digestive enzymes while endocrine cells, including insulin-producing beta-cells, secrete hormones that regulate glucose homeostasis. The proportional quantity of the different pancreatic cell populations is well defined, when exocrine cells encompass majority of the tissue mass. However, while the establishment of pancreas cellular composition during embryogenesis has been well acknowledged, its regulation is far from being elucidated. While cell intrinsic cues were shown to influent this process in the developing pancreas, the role of extrinsic signals is less understood. I hypothesize that extrinsic cues define the rate of cell proliferation and therefore govern the sizes of various pancreatic cell populations in vivo. Here I will use a novel transgenic mouse model I have recently developed, the Nkx3.2-Cre mouse line, as a tool to evaluate extrinsic roles in the regulation of pancreas cellular composition. I will further use this tool to elucidate the extrinsic cues playing a role in this process. To this end, I will deregulate signaling pathways in the pancreatic mesenchyme, a key component of the embryonic pancreas microenvironment. I will focus on two such pathways, the Hedgehog and the Wnt pathways, which are required for normal mesenchymal gene expression. I expect their deregulation will hamper mesenchymal ability to promote appropriate pancreatic cellular composition, and will enable the identification of extrinsic cues required for this process. The findings of this study will allow better understanding of the extrinsic requirements during pancreas development, and the cues governing its cellular composition. Furthermore, this study will aid current affords to expand beta-cells upon will, as a potential cure to diabetes.

  Complicit Organisations

1 Israeli organisation participates in EmPanMes.