Promoting Ectopic Pancreatic Fates: Pancreas Development and Future Diabetes Therapies

Overview

Journal Clin Genet

Specialty Genetics

Date 2008 Sep 12

PMID 18783407

Citations 6

Authors

E J Pearl

M E Horb

Affiliations

Soon will be listed here.

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).

Citing Articles

Challenges for molecular diagnosis of familial early-onset diabetes in unexplored populations.

Amara A, Chadli-Chaieb M, Chaieb L, Saad A, Gribaa M Iran J Public Health. 2015; 43(7):1011-3.

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Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells.

Oropeza D, Horb M Genesis. 2011; 50(3):271-85.

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Small-molecule inducers of insulin expression in pancreatic alpha-cells.

Fomina-Yadlin D, Kubicek S, Walpita D, Dancik V, Hecksher-Sorensen J, Bittker J Proc Natl Acad Sci U S A. 2010; 107(34):15099-104.

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Xenopus insm1 is essential for gastrointestinal and pancreatic endocrine cell development.

Horb L, Jarkji Z, Horb M Dev Dyn. 2009; 238(10):2505-10.

PMID: 19705447 PMC: 2921606. DOI: 10.1002/dvdy.22071.

The tetraspanin Tm4sf3 is localized to the ventral pancreas and regulates fusion of the dorsal and ventral pancreatic buds.

Jarikji Z, Horb L, Shariff F, Mandato C, Cho K, Horb M Development. 2009; 136(11):1791-800.

PMID: 19403659 PMC: 2680106. DOI: 10.1242/dev.032235.

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