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).

Figure 1. From pre-pancreatic endoderm to pancreas

A schematic diagram outlining the major developmental steps involved in creating different pancreatic cell types. Important progenitors are inlcuded along with genes important in key steps in pancreas development.

Figure 2. Creating a new pancreas, the future of diabetes therapy

Many future diabetes therapies revolve around the idea of creating new pancreas cells. There are two major ways to do this. Transdifferentiation involves changing a differentiated cell type into β cells by turning on pancreatic transcription factors in non-β cells. The other method is guiding stem cells (either from adult or embyronic tissue) to become pancreatic β cells utilizing combinations of growth factors and chemicals.