Genes, Signals, and Lineages in Pancreas Development

Abstract

Type I diabetes results from the autoimmune-mediated destruction of pancreatic beta cells, which regulate blood sugar levels by secretion of insulin. Recent clinical data suggest that the disease could be cured if an adequate supply of new beta-cells were available, and one goal of pancreatic developmental biology is to understand how endogenous beta-cells are made, with the hope of making them exogenously. Much is now known about the transcriptional regulation of pancreatic organ specification, growth, and lineage allocation; less is known about intercellular signals that regulate this process, but candidates continue to emerge. Additional insights, often contradicting older models, have come from the application of new lineage-tracing techniques. Altogether, these studies also shed light on the still-elusive pancreatic stem cell, which may participate in normal organ maintenance as well as recovery from injury. A rigorous proof of the existence of such a cell, whether in vivo or in vitro, would offer real hope for the prospect of controlled beta-cell generation in a clinical setting.

Foregut Mesenchyme Contributes Cells to Islets during Pancreatic Development in a 3-Dimensional Avian Model

“…It is clear that in order to find a cell source that is usable in some controlled way, it will be necessary to have a better understanding of normal embryonic islet development. 4,[41][42][43] If mesenchyme does indeed contribute cells to the definitive pancreatic epithelia, the proliferative capacity and pluripotency of fibroblasts, 44 the predominant adult cell type from mesenchyme, would suggest that pancreatic mesenchyme could be a promising source of pancreatic progenitor-or stem-cells. This possibility is further raised by reports that foetal human pancreatic mesenchyme contains cells that exhibit stem-cell like characteristics.…”

“…1,2 However, one of the main obstacles to islet transplantation being more readily available is the worldwide shortage of human pancreatic donors. Alternative sources of β-cells 3,4 are therefore required, and stem-or progenitor-cells may offer such an alternative. In order to identify these stem-or progenitorcells, however, it is essential that the normal development of the pancreas is more fully elucidated.…”

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…The pancreas originates from two patches of epithelium in the duodenum during the fifth week of gestation in humans. The endocrine pancreatic cells begin to differentiate very system are discussed in section 3.6.3. soon after the pancreas begins to bud (Murtaugh & Melton, 2003). These endocrine cells then delaminate from the epithelium and aggregate into islets.…”

“…These endocrine cells then delaminate from the epithelium and aggregate into islets. The transcription factors SOX17, PDX1, HLXB9, and PTF1a are known to be essential for normal pancreatic development based on knockout mouse models (Murtaugh & Melton, 2003). It is during the second half of gestation that the endocrine cells begin to differentiate into the specialized cell types containing a single hormone (Hellerstrom & Swenne, 1991).…”

Endocrine pancreas development in zebrafish

“…Conversely, low blood sugar levels lead to glucagon secretion by α cells to stimulate the breakdown of glycogen into glucose. [1][2][3] Somatostatin and pancreatic polypeptides act as inhibitory paracrine regulators of insulin and glucagon secretion. Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic β cells.…”