Developmental Molecular Biology of the Pancreas

Abstract

Pancreatic organogenesis is a complex and coordinated process that generates a compound gland of exocrine tissue composed of acini and ducts and endocrine tissue organized in islets of Langerhans. Both tissues originate from the same early endodermal epithelium through cell-cell signaling exchanges with adjacent tissues, including associated mesenchyme that directs a cascade of transcriptional regulatory events. Current research is aimed at elucidating the formation of pancreatic cell types and the molecular mechanisms that shape the anatomy and physiology of the pancreas. Insights into these questions come from a combination of mouse and human genetics and, increasingly, pluripotent stem cell-based models of organogenesis. These studies have identified both intrinsic factors, such as transcriptional regulators, and extrinsic signaling factors, such as secreted growth factors, morphogens, and cell-surface ligands, as determinants of cellular fate decisions, proliferation, or differentiation. The interplay between organ-restricted intrinsic factors and widely used extrinsic factors guides the stepwise process of pancreatic development from early endodermal patterning and specification of the initial pancreatic field to expansion of pools of progenitors, resolution of individual cell types, and the differentiation of mature exocrine and endocrine cells. A better understanding of pancreatic development is proving useful for comprehending the regulatory defects that drive pancreatic carcino-genesis and for devising effective therapies to correct those defects.