The pancreas is a compound organ consisting of two tissue types: the endocrine pancreas and the exocrine pancreas. The endocrine pancreas is organized into the Islets of Langerhans, which are responsible for producing hormones that control blood glucose levels. Four distinct cell types exist in the endocrine pancreas: α-cells secrete glucagon, β-cells secrete insulin, δ-cells secrete somatostatin, and PP-cells secrete pancreatic polypeptide. The islets make up a small fraction of the total pancreas mass (about 1-2%). Within the islets, β-cells make up the majority cell type and form a core structure around which other cell types are arranged.
The majority of the total organ mass is the exocrine pancreas. It is organized into acini, which secrete digestive proenzymes such as amylase, elastase, and carboxypeptidase. These enzymes are activated by cleavage and then transported through an elaborate ductal network into the small intestine to help food digestion. Within each acinus exist 30-60 acinar cells that are highly organized and form a polarized structure. The basal area of acinar cells contains a round nucleus and the rough endoplasmic reticulum (rough ER). The apical portion is filled with zymogen granules which contain the proenzymes and are required for enzyme transport and exocytosis. The polarized structure of acinar cells facilitates the regulated secretory process that occurs in a time sequence along intracellular compartments: protein synthesis, intracellular transport and sorting, secretory granule formation and exocytosis.
Fig.1 Histology of the pancreas
Organogenesis of the pancreas
In mouse embryonic development, organogenesis of the pancreas occurs during embryonic day 8.5 (E8.5) to E9.5, featured by the outgrowth of two buds (dorsal and ventral) from the endodermal epithelium located in the region of the foregut. By E12.5, the two buds develop into two primordial pancreas organs containing primarily undifferentiated epithelial cells. Shortly after this the two buds fuse to form a single organ. Starting from E14.5, acinar cells expressing exocrine markers, such as amylase, begin to emerge from the ductal epithelium. By E15.5 organized acinar structures are clearly visible. Endocrine cells coexpressing the endocrine markers glucagon and insulin appear early in development (E9.5), but they exist only as single cells dispersed in the ductal epithelium until E14 when they begin to undergo extensive proliferation. Mature islet structures organize following birth where they undergo additional remodeling.
The early budding process of the pancreas requires its interactions with growth factors secreted by the mesodermal mesenchyme and by the vascular endothelium. It is well recognized that early stages of dorsal pancreatic development require close proximity to the notochord. Removal of the notochord in early embryogenesis prevents the development of the prepatterned endodermal cells that are destined to become the dorsal pancreas. Studies have shown that the notochord secretes growth factors, such as activin-β and fibroblast growth factor 2 (FGF2), which in turn represses the Sonic Hedgehog (SHH) signaling pathway and allows ex
Transcription factors in pancreas development
The differentiation and maturation of different cell types within the pancreas is achieved by a tightly regulated transcriptional network. Most of the transcription factors involved in this process are expressed at multiple time points, play more than one role, and regulate the ex
Pdx1, also known as IPF1, IDX1 and STF1, is a homeobox transcription factor that is expressed as early as E8.5 in the primitive forgut endoderm. At E9.5, ex
The bHLH protein p48 was originally discovered as a subunit of the PTF1 complex. Together with one class I bHLH protein and RBP-Jκ, p48 forms a trimeric protein complex and activates the transcription of acinar cell specific genes such as elastase and amylase. p48 is thought to function to initiate acinar cell differentiation, which starts at around E14, although its ex
Neurogenin3 (Ngn3) is a key bHLH transcription factor that functions in the specification of endocrine progenitor cells during early embryogenesis. Its ex