Pancreas organogenesis: The interplay between surrounding microenvironment(s) and epithelium-intrinsic factors

During embryonic development, pancreatic epithelial cells engage in concomitant morphogenetic and fate specification events that will give rise to the final organ architecture and functions. Cues from the surrounding microenvironment are known to influence the behavior of epithelial progenitors and orchestrate these concomitant events throughout pancreas development. Nevertheless, the composition of the pancreatic microenvironment remains elusive; also, the interplay between components of the surrounding microenvironment and the epithelium is poorly characterized. We present here a comprehensive overview of the pancreatic microenvironment and what is known regarding distinct cell types, signaling molecules, ECM, that constitute it. We focus on the molecular circuits governing cell-cell interactions, which are at play in the developing pancreas, controlling pancreatic progenitor proliferation, morphogenesis, and differentiation. Finally, open questions and implication of future research in this field are discussed in the context of pancreatic diseases, such as diabetes and cancer, as well as therapeutic approaches for these diseases.