Cutting the edge between cancerogenesis and organogenesis of the pancreatic endocrine lineage allocation—comprehensive review of the genes Synaptotagmin 13 and 533041C22 Rik in epithelial-to-mesenchymal transition

In the past years, a multitude of studies has been published in the field of pancreatic organogenesis to interrogate the critical regulators of endocrine lineage segregation. Preliminary, transcription factors are guiding the transcriptional hierarchy of the endocrine specified cells, underpinning the importance of open chromatin formation. Signaling pathways either inhibit or accelerate the transcriptional landscape of pancreatic organogenesis. Thus, the fine-tuned process in the former pancreatic multipotent progenitors in the mechanism of lineage segregation needs to be elucidated more precisely for unraveling the temporal-spatial lineage-determining factors. Previously, Willmann et al. described candidate gene regulators of lineage segregation during the secondary transition of pancreatic organogenesis. At embryonic stage (E) 12.5, the former multipotent pancreatic progenitor compartmentalizes into the acinar, ductal, and endocrine lineage. In the adult pancreatic gland, acinar cells secrete enzymes that are transported by the duct to the duodenum. In contrast, the endocrine cells are clustered within the acinar tissue in the Islets of Langerhans. These Islets of Langerhans consist of a subset of α, δ, ε, and PP cells and β cells, and the function of the α and β cells is predominantly described by regulating glucose homeostasis, contrary, the function of the additional subtypes in the Islets of Langerhans remains still unclear and is rather pointing to a supportive role for the α and β cells. The essential wave of endocrine precursor cells emerges at E 14.5 out of the ductal cord-like structure in a process called epithelial-to-mesenchymal transition (EMT). This EMT is a reversible and incomplete process that includes significant intermedia states. As EMT is in focus in the field of cancer research, missense in endocrine lineage segregation is linking to a progression of pancreatic cancer, to be more precise in adenocarcinoma, e.g., meaning pancreatic ductal adenocarcinoma. Thus, the previous review will further accelerate the understanding of EMT about endocrine lineage segregation, respective pancreatic ductal adenocarcinoma, and introduces factors previously only known for either lineage segregation or related in cancer disease into a complete picture.