MOLECULAR ASPECTS OF LENS CELL DIFFERENTIATION 



John Papaconstantinou^ 



Department of Zoology, The Institute of Cellular Biology, 

 The University of Connecticut, Storrs, Connecticut 



I. Introduction 



We spent the first session of this workshop 

 discussing some of the molecular aspects of 

 early embryonic differentiation. Through these 

 discussions it has become obvious that one of 

 the major problems confronting the investigators 

 studying the mechanisms of cellular differen- 

 tiation is how developing cells acquire specific 

 biochemical characteristics and how these are 

 linked to morphological development and cellular 

 function. It is now well documented that as cells 

 progress through specific stages of differentia- 

 tion new biochemical traits can be acquired and 

 some existing traits can be lost. Thus, during 

 differentiation there occurs a progressive cell- 

 ular diversification which is characterized mor- 

 phologically by cellular structure and biochem- 

 ically by the synthesis of specific structural 

 proteins and enzymes. The ultimate form of 

 morphological and biochemical specialization 

 may be seen in the muscle cell, erythrocyte, 

 lens cell, etc., which synthesize tissue specific 

 proteins in the form of myosin, hemoglobin and 

 crystallins, respectively. This ability of cells 

 to lose and acquire specific biochemical charac- 

 teristics during differentiation is attributed to 

 differential gene action. The mechanisms by 

 which vertebrate cells can regulate genetic 

 expression are not known; however, it is these 

 mechanisms which are believed to be funda- 

 mental to the regulation of morphogenesis. One 

 of the approaches to the study of these mecha- 

 nisms is through studies on the regulation of 

 synthesis of tissue specific proteins as cells 

 become more highly differentiated. This after- 

 noon I would like to start the session by describ- 

 ing a system in which the regulation of synthesis 

 of specific proteins is associated with a specific 

 stage of cellular differentiation, i.e., the dif- 

 ferentiation of the lens epithelial cell to the 

 fiber cell. In addition, I would like to describe a 



series of changes in the nucleic acids (RNA and 

 DNA), also associated with fiber cell formation 

 and possibly associated with the regulation of 

 protein synthesis. Our studies have been cen- 

 tered, therefore, on the occurrence of protein 

 and nucleic acid changes associated with a 

 specific stage of lens cell differentiation. Before 

 proceeding to discuss our biochemical data I 

 would like to go over the morphological changes 

 which occur in these cells and then associate 

 these changes with the biochemical events. 



n. Morphological Changes in Fiber Cell 

 Differentiation 



A. Structure of the lens 



The lens is an avascular tissue composed 

 of the following distinct cell types: (a) an outer 

 single layer of epithelial cells; (b) a zone of 

 elongation, composed of cells which are in the 

 process of developing into fiber cells; and (c) 

 the inner fiber cells (Fig. 1). Initiation of the 

 differentiation of epithelial cells to fiber cells 

 occurs at the peripheral or equatorial zone of 

 the lens. It is in this region where the gross 

 morphological changes associated with fiber 

 cell differentiation occur, i.e., the transition 

 from a cuboidal lens epithelial cell to the 

 elongated fiber cell. After the embryonic lens 

 has been formed, fiber cells are continuously 

 laid down throughout the pre-natal and post- 

 natal life of the animal. The bulk of the lens 

 is composed of layer upon layer of these fiber 

 cells, and this continuous formation of fiber 

 cells accounts for the growth of this tissue. 

 It can be seen, therefore, that (a) secondary 



^ present address: Biology Division, Oak Ridge National 

 Laboratory, Oak Ridge, Tennessee. 



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