I have presented a series of observations on macromolecular interactions which occur during the terminal stages of lens cell differentiation. These are summarized in Fig. 2. Other cell types that undergo similar changes are the erythrocyte and skin cells (epidermis) during the process of keratinization. These other cells are also involved in the synthesis of highly specific proteins, and there are indications that molecular alterations similar to those described for the lens may also occur in these cells (26). Thus, elucidation of a specific series of macromolecular interactions such as those described may provide a basis for the biochemical definition of the terminal stages of cellular differentiation. Differentiation of the reticulocyte, for example, involves inactivation of the nucleus, stabilization of mRNA, and possibly a ribosomal breakdown such as I have described here (26). Furthermore, elucidation of the mechanisms of reactions involving the initiation of tissue-specific protein synthesis and subsequent nuclear inactivation, stabilization of mRNA, and breakdown of the ribosomes may provide a basis for defining the mechanisms of terminal cellular differentiation. The lens cell has reached its highest form of cellular differentiation when it has formed the fiber cell. With respect to the mechanism of lens fiber cell formation, we would like to know whether specific biochemical changes such as γ-crystallin synthesis are intimately linked to fiber cell formation - that is, whether γ-crystallins are required to bring about the formation of a fiber cell. The potential for synthesizing γ-crystallins is inherent in the genome of the cell. This part of the genome is nonfunctional in the epithelial cell. Can these genes be activated without bringing about a simultaneous cellular elongation, nuclear inactivation and loss of cellular replication, stabilization of mRNA, and breakdown of the ribosomes? The degree of coupling or uncoupling of tissue-specific-protein synthesis to morphogenesis is an important part of the mechanism of cellular differentiation. We feel that we have now reached the stage where we can begin to answer these questions.
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