A Hierarchy of Self-Limiting Reactions as the Basis of Cellular Differentiation and Growth Control

An hypothesis of cellular differentiation based upon the differentiation of cytoplasmic particles similar to tumor agents and differentiating like the surface antigen system in Paramecia as demonstrated by Sonneborn is suggested. Various facts are assembled and used as the basis for a suggested mechanism of pattern formation. Differentiation as it proceeds from a center of organization, seems to occur not as the result of release of a series of specific inductors, but by the release of a general stimulus upon which is superimposed a series of specific inhibitions. One universal characteristic of differentiating systems is a progressive loss of potency. The loss increases with time and with distance from a center of organization. The center is characterized by higher general metabolism than any other qualitatively similar locus, and is the first region to do certain things. Once an organization center has become active, other less rapidly developing regions are inhibited and do not attain the high level of differentiation proceeding in the center. It is suggested that differentiation consists of the successive inhibition of one gene-initiated reaction after another by the collection of specific metabolites which inhibit in the mass-action relationship. A major assumption in the hypothesis is that there are specific metabolites which in sufficient concentration will inhibit differentiation of the cell type which produced them. An initial test seems to support this view. Bloodless, heartless and nerveless tadpoles have been produced by culturing embryos with either living adult blood cells, or pieces of heart or pieces of brain in the medium.