Early pancreas organogenesis: Morphogenesis, tissue interactions, and mass effects

Abstract

The midgut region and adjacent tissues of mouse embryos acquire the ability to form exocrine pancreas tissue in vitro at about the 8-somite stage. By 10 somites a region of the gut itself can be identified as the precursor of the pancreas. The endoderm of this area apparently becomes committed or determined by about 15 somites, since at that time it can form exocrine acini when combined with mouse salivary mesoderm. These alterations occur at stages before condensed pancreatic mesoderm is present or before outgrowth of the pancreas diverticulum occurs. The beginning of pancreatic morphogenesis is marked by appearance of a broad-based upswelling from the dorsal gut. The base of this evagination gradually constricts to give rise to the pancreatic duct. These, and results on the distribution of mesodermal and endodermal cells during early organogenesis, are discussed in relation to the concept that a primary commitment or determination phase is followed by a secondary support phase during which nonspecific mesodermal input is sufficient to permit tissue growth. The role of such growth, as reflected in epithelial mass, was also investigated. Precocious appearance of zymogen granules or amylase is not evoked by even a 24-fold increase in mass of primitive mouse pancreatic epithelium. On the other hand, fractionation of growing epithelia, with resultant decrease in tissue mass, leads to postponement of overt differentiation. Once cells have reached a specific chronological age, they differentiate if left in an undisturbed tissue mass for about 2–3 days. Under such circumstances, differentiation can occur in extraordinarily small tissue masses. Mass per se is not the critical factor leading to cessation of mitosis and commencement of over cytodifferentiation. Operationally, the cells must be sufficiently mature and must be undisturbed, in the sense of not being stimulated to continue dividing, if differentiation is to occur.