292 The Nature of Biological Diversity 



notion of the biochemical changes which take place in ganglia con- 

 fronted with an enlarged peripheral field such as the one provided 

 by an additional limb bud. We know that the mitotic activity increases 

 and as a consequence more nerve cells are produced. The effect ic 

 restricted to the ganglia which contribute fibers to the graft. This is 

 in fact the main difference between the effects elicited by a trans- 

 planted limb and an implanted tumor. There are, however, instances 

 of moderately active tumors where the effect is restricted to the 

 ganglia which send fibers into the neoplastic tissue. The difference is 

 therefore more of a quantitative than of a qualitative order. The 

 massive and generalized effects elicited by rapidly growing tumors, or 

 by injection of large quantities of the salivary NGF, represent excep- 

 tional events with no parallel in the normal development of the 

 embryo. Under normal conditions, it seems conceivable that the 

 peripheral end organs release small quantities of growth factors and 

 that these factors may utilize the nerve fibers as channels of diffusion 

 to the associated nerve centers. This hypothesis would explain the 

 mitotic effects and at the same time would not be in conflict with the 

 observation that the effects are restricted to nerve centers contributing 

 fibers to the implanted organs. 



In suggesting that the effects evoked by peripheral structures and 

 by the NGF isolated from tumor, snake venom, and the mouse salivary 

 glands might in ultimate analysis operate in a similar way, we wish 

 to make clear that the growth factors need not be the same in all 

 experimental conditions examined above. It was in fact shown that the 

 effects elicited by the transplantation of an additional limb are mainly 

 apparent on the V-L sensory cells while the effects of the tumor and 

 of the purified NGF are mainly and perhaps entirely restricted to 

 the M-D cells and to the sympathetic ganglia. 



A confirmation of the above hypothesis would come from the isola- 

 tion of growth factors from peripheral structures with a specific effect 

 on other nerve cells, such as the V-L sensory cells and the motor 

 neurons. This is one of the problems we propose to investigate. The 

 realization that it is a very difficult problem makes it more challenging 

 and worth the efforts it will require. 



References 



1. J. F. Tello (1922), Les differenciations neuronales dans 1'embryon du poulet 

 pendant les primiers jours de l'incubation, Trav. Lab. Rec. Biol., Univ. Madrid, 

 T., 21:1-93. 



2. W. F. Windle and D. W. Orr (1936), Neurofibrillar development in the central 



