Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies

Abstract

Diabetes is a disease that could be treated more effectively with a better understanding of pancreas development. This review examines the role of master regulator genes driving crucial steps in pancreas development, from foregut specification to differentiation of the five endocrine cell types. The roles of Pdx1, Ptf1a, and Ngn3 are particularly examined as they are both necessary and sufficient for promoting pancreatic cell fates (Pdx1, Ptf1a) and endocrine cell development (Ngn3). The roles of Arx and Pax4 are studied as they compose part of the regulatory mechanism balancing development of different types of endocrine cells within the iselts and promote the development of alpha/PP and beta/delta cell progenitors, respectively. The roles of the aforementioned genes, and the consequences of misexpression of them for functionality of the pancreas, are examined through recent studies in model organisms, particularly Xenopus and zebrafish. Recent developments in cell replacement therapy research are also covered, concentrating on stem cell research (coaxing both adult and embryonic stem cells toward a beta cell fate) and transdifferentiation (generating beta cells from other differentiated cell types).