Regulation of specific protein synthesis in cytodifferentiation.

Abstract

The developmental features of the pancreas are reviewed as an 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) 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 vitro 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.