Proliferation and Differentiation of Pancreatic Progenitor Cells
This research focuses on the development of pancreatic islets during embryogenesis and early stages of postnatal life, which requires complex patterning information controlling fundamental cellular processes, such as differentiation and proliferation of endocrine progenitor cells.
The objective of this research is to understand the mechanisms that control the proliferation of endocrine progenitor cells in the formation of a functional endocrine pancreas. We have identified several cell-cycle component genes that are specifically expressed in endocrine progenitor cells and appear to play key roles in the formation of mature islets. We will address the role of these genes in maintaining a balance between proliferation of progenitor cells, and differentiation of endocrine cells.
Several approaches will be used, including: genetic analysis of mutant mouse strains that lack cell cycle regulators, development of cell-type-specific inducible transgenic mice, as well as, in vitro explant cultures to study islet morphogenesis during embryogenesis and functional maturation of islets during postnatal development to maintain normal glucose homeostasis. Understanding the details of how proliferation and differentiation of endocrine cells is regulated during islet development will be essential for devising methods for islet regeneration, or for generating endocrine cells in culture for islet transplantation studies.