Regulation of specific protein synthesis in cytodifferentiation

Abstract

The developmental features of the pancreas are reviewed as a n example of cytodifferentiation and organogenesis. Attention is directed to the regulatory characteristics of the specific proteins synthesized and secreted by the endocrine and exocrine cells. The following topics are discussed: (1) The number of specific protein species and, inferentially, the number of genes involved in differentiated function.( 2 ) The stringent regulation of the concentration of these specific proteins and the probable restriction of their synthesis to exocrine and endocrine cells. (3) The multiphasic pattern of accumulation of these specific proteins during pancreatic development and the synchronized but noncoordinate regulation of individual protein species. Synthetic rates of specific exocrine proteins in uit70 correlate closely with measurements of the accumulation of proteins during development. (4) A model postulating three regulatory transitions. The primary transition (related to organ "determination") denotes the conversion of a "predifferentiated" cell to the "protodifferentiated" state in which low but significant levels of specific proteins are present. The secondary transition is viewed as an amplification of this specific protein synthesis and is associated with typical pancreatic histogenesis. In the third regulatory transition, the synthesis of specific proteins in the "differentiated state" is modulated by diet, or hormonal states, etc. The third regulatory transition may be similar to some types of "enzyme induction" as studied in multicellular systems. (5) The differentiative fidelity in an organotypic culture system; the role of mesenchymal tissue or a particle fraction derived therefrom in supporting the protodifferentiated state and the secondary regulatory transition. (6) The possible mechanisms of the secondary regulatory transition in exocrine cells. Effects of actinomycin D, bromodeoxyuridine, and other mitotic inhibitors suggest the requirement for a critical cell division prior to the loss of proliferative capacity. (7) The synthesis of pro-insulin and insulin during primary and secondary regulatory transitions; the possible interrelationships of endocrine and exocrine cells in pancreas development.Embryological development may be viewed as the formation of cells of different phenotype from common genotypic precursors. Since the basic physiological and morphological features of cells are largely a result of their protein (enzyme) complement, the mechanisms involved in development are reduced largely to the qualitative and quantitative regulation of the proteins of the system. There have been two major lines of investigation contributing to our understanding of the processes involved in embryological development. The f i s t is concerned with the mechanism of "embryonic induction," in which a heterotypic cellular interaction results in a complex series of developmental events usually including alterations in cell proliferation, morphogenesis, and a grossly modified pattern of protein synthesis. T...

Proteins synthesized and secreted during rat pancreatic development.

“…During the next 3-4 d, acinar structures form and the low levels of exocrine secretory proteins and insulin are maintained ("protodifferentiated state") (22, 23) . A second differentiative transition is detectable beginning at 14-15 d gestation when there is a rapid increase in rough endoplasmic reticulum, a 103-to 10'-fold increase in the accumulation of the specific exocrine enzymes and insulin, coupled with the appearance of zymogen granules in acinar cells and,8 granules in B cells (4,21,23) accumulate in a parallel fashion but slightly preceding the secretory proteins (10,11,20) .We have now used two-dimensional gel electrophoresis to monitor protein synthesis and secretion during development of the embryonic pancreas . This method allows analysis of both the pancreas-specific products (the secretory (projenzymes) and the synthetic patterns of the total proteins .…”

“…These proteins are not detected in the adult pancreas or in zymogen granules but are also released by several other embryonic tissues. The function of this set of proteins is unknown .Pancreatic differentiation has been extensively studied at both morphological (18, 19) and biochemical levels (5,14,23,25). Normal development requires interaction between epithelial and mesenchymal tissues (8,25).…”

“…Normal development requires interaction between epithelial and mesenchymal tissues (8,25). Early investigations suggested that pancreatic differentiation is a multiphasic process (4,21,23) . In the rat, the formation of the pancreatic rudiment from the gut at -11 d gestation is coupled to the appearance of very low levels of exocrine proteins and insulin (the primary transition) .…”

“…Pancreatic differentiation has been extensively studied at both morphological (18, 19) and biochemical levels (5,14,23,25). Normal development requires interaction between epithelial and mesenchymal tissues (8,25).…”

“…In the rat, the formation of the pancreatic rudiment from the gut at -11 d gestation is coupled to the appearance of very low levels of exocrine proteins and insulin (the primary transition) . During the next 3-4 d, acinar structures form and the low levels of exocrine secretory proteins and insulin are maintained ("protodifferentiated state") (22,23) . A second differentiative transition is detectable beginning at 14-15 d gestation when there is a rapid increase in rough endoplasmic reticulum, a 103-to 10'-fold increase in the accumulation of the specific exocrine enzymes and insulin, coupled with the appearance of zymogen granules in acinar cells and,8 granules in B cells (4,21,23).…”