Gene regulatory factors in pancreatic development

Abstract

The intensity of research on pancreatic development has increased markedly in the past 5 years, primarily for two reasons: we now know that the insulin-producing ␤-cells normally arise from an endodermally derived, pancreasspecified precursor cell, and successful transplants of islet cells have been performed, relieving patients with type I diabetes of symptoms for extended periods after transplantation. Combining in vitro ␤-cell formation from a pancreatic biopsy of a diabetic patient or from other stem-cell sources followed by endocrine cell transplantation may be the most beneficial route for a future diabetes therapy. However, to achieve this, a thorough understanding of the genetic components regulating the development of ␤-cells is required. The following review discusses our current understanding of the transcription factor networks necessary for pancreatic development and how several genetic interactions coming into play at the earliest stages of endodermal development gradually help to build the pancreatic organ.

Global gene expression profiling and histochemical analysis of the developing human fetal pancreas

“…Our current knowledge of transcriptional regulation of mammalian pancreatic development is largely derived from studies on mice, in which gene regulation can be manipulated in a conditional and tissue-specific manner to provide information on signalling pathways and cell lineage [23]. The evagination of the human foregut to form the ventral and dorsal pancreas takes place around 4-5 weeks post coitum (Carnegie stage 12-15) corresponding to mouse embryonic day (E)9.5 (six to ten somites) [24,25].…”

Pancreas organogenesis: From bud to plexus to gland

“…In accordance with models for heterologous organ development processes in several species, the spatiotemporal expression pattern of such TFs, and their levels, are tightly controlled in normal pancreatogenesis. Because most of the studies of the above TFs have been extensively reviewed elsewhere (Jensen, 2004;Jorgensen et al, 2007;Oliver-Krasinski and Stoffers, 2008;Gittes, 2009), we focus here only on a few instructive examples, focusing on newly discovered roles in early MPC formation and maintenance, as well as highlighting some that are noticeably understudied and deserving future attention.…”

HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion

“…Thus it was a logical candidate for a regulatory role in the reprogramming of the insulin gene program in hybrid cells. Hes1 is the key downstream effector of the Notch signalling pathway in β-cells [11]. To determine if Hes1 was significant in regulating the differentiation state of pancreatic cell lines, we performed quantitative real-time RT-PCR on RNA from the parental cell lines MIN6 and βlox5, revealing that the non-insulin-producing βlox5 cells had Hes1 transcript levels 10-fold higher than insulin-producing MIN6 cells relative to GAPDH, using a set of primers that detected both human and mouse GAPDH ( Fig.…”