Differentiation: "Keep the Genome Constant but Change over and over again its Ionic and/or Macromolecular Environment"? A Conceptual Synthesis.

The unifying concept that differentiation in animals is the stepwise formation of cells or cell clusters which differ primarily in their plasma membrane-cytoskeletal properties and which mostly become organised into a variety of epithelia, lining different compartments, is formulated. As a consequence of these differences in plasma membrane-cytoskeletal complex properties - this causal relationship being the very point - the distinct emerging cell types will be able to display a differential pattern of protein synthesis, cellular morphology and physiology, notwithstanding the fact that they have identical genomes and similar basic mechanisms of protein synthesis and processing. Differences in the plasma membrane-cytoskeletal complex, of which the structure furnishes the cells with a differential three-dimensional molecular scaffold, are usually achieved first and are of necessity followed by differential protein synthesis and pattern formation. This can be also succinctly stated as : form precedes function. In addition to this widely used principle, secondary mechanisms for controlling the expression of specific genes in specific cell types may operate. The major <<strategy>> used in differentiation of somatic cells seems to be to keep the genome constant (GURDON'S experiments, 1962) but to change its <<environment>> over and over again. This environment comprises two sets of constituents, ionic and macromolecular ones, acting in complementary ways. The first one may be more appropriate for the coarse tuning of gene expression/protein synthesis and the second (especially the trans-acting factors) for the fine tuning. Consideration of animal development in terms of differential epithelium formation may make a major contribution to the unification of developmental biology of animals.