Linked Programs of Epithelial Morphogenesis and Cell Fate in the Pancreatic Endocrine Progenitor Niche
Bankaitis, Eric Daniel
During mouse embryogenesis, organ formation is accomplished through a close coordination between genetically encoded programs of proliferative growth, differentiation, and morphogenesis in organ-specific progenitor populations. In the developing pancreas, hormone-secreting endocrine cells arise from a pool of bipotent duct/endocrine progenitors located within the ‘trunk’ epithelium. While much is known about the transcription factors and signaling pathways that maintain bipotent progenitors in an undifferentiated state, or that guide cells toward differentiated cell lineages, it is unknown how these transcriptional and signaling inputs are patterned and deployed within the developing trunk to regulate cell-fate allocation, and ultimately, to determine the structure and composition of the mature organ. Here, we adapt concepts developed from studies on the stem-cell niche, and apply them to organ development to gain a better understanding of how growth, differentiation, and morphogenesis programs are linked within organized ‘units’ of pancreatic progenitor cells. We combine three-dimensional mapping approaches with genetic and pharmacological interference tests to dissect how the architecture and morphogenesis of the trunk epithelium influences, and is influenced by, the genetic programs that regulate the balance between progenitor maintenance versus endocrine lineage-differentiation. These studies identify and begin to functionally characterize an endocrine progenitor niche that guides the genesis of the duct and endocrine pancreas.