XB-ART-38350Clin Genet October 1, 2008; 74 (4): 316-24.
Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies.
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).
PubMed ID: 18783407
PMC ID: PMC4025910
Article link: Clin Genet
Genes referenced: arx egf hes1 lif neurog3 pax4 pdx1 ptf1a
GO keywords: enteroendocrine cell differentiation
Disease Ontology terms: glucose metabolism disease
OMIMs: DIABETES MELLITUS, NONINSULIN-DEPENDENT; NIDDM
Article Images: [+] show captions
|Fig. 1. From pre-pancreatic endoderm to pancreas. A schematic diagram outlining the major developmental steps involved increating different pancreatic cell types. Important progenitors are included along with genes important in key steps inpancreas development.|
|Fig. 2. Creating a new pancreas, the future of diabetestherapy. Many future diabetes therapies revolve around theidea of creating new pancreas cells. There are two majorways to do this. Transdifferentiation involves changinga differentiated cell type into b cells by turning on pancreatictranscription factors in non-b cells. The other method isguiding stem cells (either from adult or embryonic tissue) tobecome pancreatic b cells using combinations of growthfactors and chemicals. ES cells, embryonic stem cells; EGF,epidermal growth factor; LIF, leukemia inhibitory factor.|