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Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies
Author(s) -
Pearl EJ,
Horb ME
Publication year - 2008
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2008.01081.x
Subject(s) - pdx1 , biology , zebrafish , pancreas , transdifferentiation , progenitor cell , enteroendocrine cell , pax4 , stem cell , microbiology and biotechnology , foregut , beta cell , cellular differentiation , cell type , embryonic stem cell , endocrine system , endocrinology , cell , genetics , hormone , diabetes mellitus , gene , homeobox , anatomy , islet , transcription factor
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 α/PP and β/δ 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 β cell fate) and transdifferentiation (generating β cells from other differentiated cell types).