Transcription Factors in Pancreatic Development

Abstract

Through the analysis of genetically modified mice a hierarchy of transcription factors regulating pancreas specification, endocrine destiny as well as endocrine subtype specification and differentiation has been established. In addition to conventional approaches such as transgenic technologies and gene targeting, recombinase fate mapping in mice has been key in establishing the lineage relationship between progenitor cells and their progeny in understanding pancreas formation. Moreover, the design of specific mouse models to conditionally express transcription factors in different populations of progenitor cells has revealed to what extent transcription factors required for islet cell development are also sufficient to induce endocrine differentiation and the importance of the competence of progenitor cells to respond to the genetic program implemented by these factors. Taking advantage of this basic science knowledge acquired in rodents, immature insulin-producing cells have recently been differentiated in vitro from human embryonic stem cells. Taken together these major advances emphasize the need to gain further in-depth knowledge of the molecular and cellular mechanisms controlling beta-cell differentiation in mice to generate functional beta-cells in the future that could be used for cell therapy in diabetes.

Pancreas-enriched miRNA refines endocrine cell differentiation

“…The endocrine differentiation program is initiated by neurogenin 3 (Ngn3), which induces a complex network of transcription factors, to specify the different endocrine lineages (Gradwohl et al, 2000;Gu et al, 2002;Martin et al, 2007;Bonal and Herrera, 2008;Lyttle et al, 2008). This process results in the differentiation of mature hormone-producing cells (Murtaugh and Melton, 2003).…”

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

“…However, it is now clear that during development, a common group of multipotent progenitor cells in the embryonic gut, expressing specific markers such as Foxa1, Foxa2, Pdx1, Ptf1a and Sox9, give rise to both the endocrine and exocrine pancreas (Burlison et al, 2008; Gao et al, 2008; Gu et al, 2002; Kawaguchi et al, 2002; Martin et al, 2007; Seymour et al, 2007). Recently, Zhou and Melton proposed a “tiptrunk” model in an effort to explain tissue dynamics during pancreas development (Zhou et al, 2007).…”

Relative roles of the different Pax6 domains for pancreatic alpha cell development

“…The development of the endocrine pancreas is governed by a cascade of transcription factors [1,2]. The first regulators are Pdx1 and Ptf1a , which initiate pancreatic bud formation from the foregut and ngn3, which separates the endocrine progenitor cells from the exocrine part of the organ.…”