New findings in pancreatic and intestinal endocrine development to advance regenerative medicine.

PURPOSE OF REVIEW: We highlight some of the major recent advances that have been made towards understanding the mechanisms that control endocrine differentiation and cell identity in the pancreas and intestine.

RECENT FINDINGS: Notch signaling plays a complex role in the fate choice between endocrine, duct, and acinar lineages in the developing pancreas. New approaches to dissecting the role of mesenchymal cells in the developing endocrine pancreas reveal inhibitory signals from the endothelium. Epigenetic mechanisms represent another layer of control over pancreatic development and β cell identity. Further details on the transcriptional control of enteroendocrine cell development have emerged and revealed a surprising role for FoxO1 in restraining insulin expression in the gut. Incremental progress is being made in the field of directed differentiation of embryonic stem cells to pancreatic β cells and the first reported differentiation of human embryonic stem cells into intestinal organoids containing enteroendocrine cells represents a major breakthrough.

SUMMARY: Greater knowledge of the fundamental processes controlling endocrine development in the pancreas and intestine has the potential to advance the field of regenerative medicine by providing a pathway to successfully create cell types of clinical interest.