Gene activity in early development / Eric H. Davidson.

  • Eric H. Davidson
Date:
[1968]
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Gene activity in early development / Eric H. Davidson. Source: Wellcome Collection.

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    DNA CONSTANCY AND DIFFERENTIATION REVERSIBILITY 5 first into phagocytotic macrophages, and then into collagen-secreting fibroblasts. This transformation was claimed to occur many years ago by Maximow (6) and others, and has since been observed in various experimental circumstances. Thus Petrakis, Davis, and Lucia (7) have shown that a culture of circu¬ lating mononuclear leukocytes sealed into a diffusion chamber is apparently able to give rise to a sheet of collageneous connective tissue fibroblasts, after passing through an intermediate macrophage stage. The identity of the col¬ lagenous fibroblasts with their macrophage precursors is certified by their retention of india ink particles originally incorporated by the macrophages. These cases, however, like most of the other examples of transformation in state of cell differentiation with which we are familiar, are vulnerable to the argument that they deal with only a small fraction of the total genomic information possessed by the organism, and thus with only a few functional traits. A priori, such traits could be regarded as closely related by virtue of the very fact they belong to the repertoire of functions normally resident in a single cell type. From a biochemical point of view this argument is scarcely persuasive in that the differences between a cell specialized for pigment synthesis and a neuron, or between a leukocyte and collagen-secreting fibro¬ blasts, would seem no less than those between a liver and a kidney cell. None¬ theless, one must have recourse to a certain amount of generalization to conclude from such cases that a differential cell nucleus actually contains the whole genome, and the case for this now rests to a large extent on other evidence. DNA constancy and the reversibility of differentiation A critical element of evidence relevant to the nature of the nuclear changes underlying cell differentiation is the presence of twice the haploid amount of DNA in the nucleus of every differentiated cell (certain particular exceptions aside), except for the gametes, which contain half the somatic cell quantity. This fact, discovered in 1947-1948 by Mirsky and Ris (8) and Boivin, Ven- drely, and Vendrely (9), has provided one of the major reasons for regard¬ ing DNA as the genetic material. Equality of DNA content among differen¬ tiated cell nuclei means that differentiation cannot in general be explained through the selective physical loss of unused DNA genes from the nucleus, but this does not preclude the possibility that differentiation involves the inactivation of DNA coding for properties not manifest in a given cell type by means of some mutationlike chemical alterations in the genetic material. The latter scheme is now virtually eliminated as well, unless the alterations in question are instantly reversible, for the experiments of Gurdon have shown that nuclei from a sizable proportion of the differentiated intestinal cells of
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