Chromosomal Organization as a Genetic Basis of Cytodifferentiation in Multicellular Organisms

Abstract

THE genetic mechanisms in differentiative phenomena of bacterial cells have recently been elucidated in great detail by the work of Jacob and Monod^1–4. However, the differentiation of cells in multicellular organisms differs in some respects from that observed in bacterial cells. The main difference is in the virtual irreversibility of the differentiation observed in metazoan cells; for example, hepatocytes never change into neurones and vice versa. This type of differentiation, that assures stable cell diversities in multicellular organisms, is apparently lacking among bacterial cells. It seems necessary to recognize this peculiar feature of the metazoan cells before we discuss the genetic mechanisms of differentiation in this system. So we designate this phenomenon of stable specialization of cells as ‘major differentiation’ of metazoan cells. On the other hand, the differentiated metazoan cells also exhibit transient modulations both in functional and structural aspects; for example, hepatocytes, after hepatectomy, change their resting state, proliferate vigorously and, after complete restoration, re-attain their former highly differentiated state. This phenomenon has often been referred to as transient de-differentiation of hepatocytes. But it is not the same as the loss of major differentiation, as the former is a completely reversible phenomenon, like the reactions of bacteria to inducer or represser substances. This type of differentiation also includes functional changes of cells. We therefore distinguish it as ‘minor differentiation’. Thus, in metazoan cells we find at least two different types of differentiation, ‘major differentiation’, which is virtually irreversible and determines cell specificity in certain tissues, and ‘minor differentiation’, which is usually reversible and related rather to functional states of the cell. The cell usually shows both types of differentiation at the same time. Cells can lose or gain the minor differentiation without changing the state of major differentiation; hepato-cytes, for example, keeping their hepatocytic specificity unchanged, can be either in a resting functional state or in a proliferating regenerative phase. These peculiar features of major and minor differentiation are the outstanding characteristics that distinguish the differentiation of metazoan cells from that of bacterial cells. They must be taken into account in considering the genetic mechanisms involved in the differentiation of multicellular organisms.