XB-ART-38350Clin Genet October 1, 2008; 74 (4): 316-24.
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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
Species referenced: Xenopus
Genes referenced: arx egf hes1 lif neurog3 pax4 pdx1 ptf1a
GO keywords: enteroendocrine cell differentiation
Disease Ontology terms: glucose metabolism disease
OMIMs: TYPE 2 DIABETES MELLITUS; T2D
Article Images: [+] show captions
References [+] :
Afelik, Combined ectopic expression of Pdx1 and Ptf1a/p48 results in the stable conversion of posterior endoderm into endocrine and exocrine pancreatic tissue. 2006, Pubmed, Xenbase