Lineage determinants in early endocrine development

► Transcription factor networks underlie primary MPC maintenance and lineage choice. ► Behavior of endocrine progenitors is closely tied to the 3D epithelial structure of the developing pancreas. ► Heightened Ngn3 expression defines endocrine commitment within the trunk epithelium. ► Islet subtype diversification and maturation involves specific transcription factor interactions and potential epigenetic inputs. ► Deeper understanding and successful mimicking of extrinsic and intrinsic interactions will improve endocrine subtype differentiation attempts in vitro.