example of this case is the nuclear trans- 

 plantation experiment donebyDr. Hammerling's 

 group between Acetabularia mediterraneae and 

 Acetabularia chronata. These experiments dem- 

 onstrate very clearly that the morphology of 

 the algae is governed by the nucleus. Here we 

 have a direct demonstration of the dominant 

 role played by the nuclear body in differentia- 

 tion. 



The next pathway, another extreme case, 

 will be called the cytoplasmic-determinant case. 

 In this situation the cytoplasm is making all the 

 decisions that are necessary and requires no 

 help from the nucleus. Experimental demon- 

 stration of this situation is to destroy the 

 nucleus or to block its pathways with an inhibi- 

 tor such as actinomycin-D. Of this situation 

 we have two subclasses. The first we shall 

 call the latent message case. Certain messages 

 are stored in the cytoplasm which are nuclear 

 in origin. These messages are latent in the 

 cytoplasm and will be called upon later when 

 needed. It appears that this is the case in the 

 development of sea urchin eggs as described 

 by Dr. Paul Gross. Perhaps to some extent a 

 similar mechanism is operating in the system 

 described by Dr. James Lovett. A detailed 

 discussion with Dr. Gross revealed that the 

 result really depends on the monitoring system. 

 In a superficial examination of the morphologi- 

 cal appearances or general biochemical data, 

 the influence of the nucleus may not be detect- 

 able, but by detailed biochemical analysis, as 

 Dr. Gross has explained to me, in the case of 

 protein synthesis the nucleus can be shown to 

 exert a considerable control over the cytoplasm. 

 The information originates in the nucleus, but 

 the cytoplasm does have the power of control 

 of the expression of this information until the 

 right time. 



The next subclass is the absolute cyto- 

 plasmic determinant case. The experimental 

 demonstration of this type is hard to describe 

 because it is foreign to our thinking on cellular 

 biology. 1 cannot present any biological example 

 of it but 1 can describe what the experimental 

 requirement is in order to demonstrate its 

 existence. We have a cell which can divide into 

 two cells or more. Each of these new cells can 

 make the decision to differentiate into various 

 cell types as A, B or C shown in Scheme II. 

 After blocking of the influence of these cells 

 by direct destruction or by inhibitor, we see 

 whether the cells can still differentiate into 

 cell type A, B or C or not. The exciting results 

 concerned with the stem cells described by 



Dr. James Till may provide an experimental 

 system for testing of this case. It should be 

 noted that this situation (Scheme II) is very 

 different from that of the reticulocyte system. 

 When cells reach the reticulocyte stage, their 

 fate has been predetermined. Demonstration of 

 Scheme II has to be done with cells which still 

 maintain their capacity to choose among vari- 

 ous paths. 



It is not easy to separate these two sub- 

 classes, i.e., the latent message case from 

 the absolute cytoplasmic-determinant case. Sui- 

 cidal experiments with radioactivity decay of 

 p32 or H3 may be helpful. With proper experi- 

 mental design, the latent message (if it is RNA) 

 can be destroyed specifically while the rest of 

 the cellular machinery is kept intact. 



The last type of pathway to be described is 

 likely to be the most common one, the perturb- 

 ation-response system. In this case a perturba- 

 tion, a challenge, arises (most probably) in the 

 cytoplasm. It receives, for instance, a hormonal 

 stimulus, it runs out substrates, or it is acti- 

 vated by an overdose of CO2, or light, etc. In 

 response, the cytoplasm transmits a signal to 

 the nucleus as another perturbation. The nucleus, 

 in response to this signal, picks up the pre- 

 inscribed genetic program, and issues a new 

 command for the cell to follow. Under these 

 circumstances, the answer to the question about 

 the exact location of the decision making body 

 is debatable. Research workers who are pri- 

 marily interested in the function of the genetic- 

 nuclear apparatus, would say that the decision 

 making body is in the nucleus, since it is the 

 nucleus that issues the new command for the 

 cell to change its course. Workers who are 

 mainly interested in cytoplasmic events may 

 claim that the cytoplasm should be called the 



r— db 



.<Aa 

 "-Db 



Nuclear attack 

 or inhibition 



Experimental requirement for the demonstration of 

 cytoplasmic determinant case 



197 



