356 



Special Vertebrate Organogenesis 



direction over another would entail a statis- 

 tical deviation of the hbers m the lavorea 

 airection — an over-ail trend rather tnaii a 

 common course. Many dendiitic iieicls, lor 

 instance, show such a trend, ihe graduax 

 detiection, rather than dehnite orientation, 

 toward the cathodal site of neurons in tissue 

 cultures exposed to electric helds of propei 

 density (Marsh and Beams, '4t>; presents all 

 the aspects of this picture, indicating simpiy 

 relative inhibition of hlopodial protrusion 

 on the anodal side with no cathodal "stimu- 

 lation" or "attraction," a view confirmed by 

 direct observations on slime moulds (Ander- 

 son, '51). These electric effects evidently 

 operate not by laying down pathways, but 

 Dy proliibiting some of the existing ones (see 

 t'lg. 48 in Weiss, '50a). 



It must be fiurther postulated that the 

 chemical characteristics of the pathway sys- 

 tems endow contact guidance with an eie- 

 ment of selectivity. It would seem impossiDie 

 otherwise to explain the fact reported below 

 that different kinds of nerve hbers tend to 

 choose different patliway systems when faced 

 with a choice. Only a faint trace of such 

 selectivity has thus far been observed in 

 tissue culture in the preference of nerve 

 tips for interfaces of tissue exudate rather 

 than of fibrin (Weiss, '45). At any rate, such 

 discriminatory ability is based on affinity 

 for the chemical constitution of the contact 

 surface rather than on the perception of 

 concentration gradients of diffusing sub- 

 stances as surmised in the theory of chemo- 

 tropism. A singularly strong affinity of this 

 kind seems to exist between axoplasm and 

 the protoplasm of the sheath cells of Schwann 

 (see p. 367), 



The described mode of advance of the 

 nerve tip makes it clear that the "rate of 

 free outgrowth" is a function of both the 

 neuron itself and the configuration of the 

 pathway system. The rates are of similar 

 magnitude whether determined in the em- 

 bryo, in nerve regeneration or in tissue cul- 

 ture (Harrison, '35b). It must be borne in 

 mind, however, that these are over-all values 

 of length over time without implying uni- 

 form speed. Actually, the advance consists 

 of alternating spurts and delays, the fre- 

 quency of the latter mounting with increas- 

 ing irregularity ("intersectedness") of the 

 substratum (see Weiss and Garber, '52). Con- 

 sequently, the total rate is fastest along 

 straight oriented pathways (e.g., during nerve 

 regeneration inside old Schwann tubes; Gut- 

 mann, Guttmann, Medawar and Young, '42) 

 and slowest in the dense and confused fiber 



tangle of a scar. The maximum rate of ad- 

 vance under optimal conditions is of the 

 order of a few millimeters per day (at 37° 

 C), which is close to the autonomous rate 

 of proximodistal movement of axoplasm ob- 

 served in the perpetual growth of neurons, as 

 described below (p. 364). Any faster elonga- 

 tion of nerve hbers (e.g., Wislocki and 

 Singer, '46) suggests passive elongation by 

 towing. 



Neurotropism. "Contact guidance," as here 

 described, is but a modified and more de- 

 tailed version of such concepts of nerve 

 orientation as have been proposed by His 

 (1887), Harrison ('14), and Dustin ('10). 

 They all imply that the nerve fiber is con- 

 ducted on its way by markings of its im- 

 mediate contact surroundings, rather than 

 directed from a distance by the tissue of 

 destination issuing "attractive" forces or 

 merely acting in the manner of a beacon. 

 Such "distance action," commonly referred 

 to as "neurotropism" and assimied to be a 

 form of either galvanotropism or chemo- 

 tropism, has been invoked to explain oriented 

 nerve growth in the embryo (e.g., Kappers, 

 '17), as well as during later nerve regenera- 

 tion (foremost: Cajal, '28; Forssman, 1900). 

 This concept dates from a period in which 

 the mechanism of nerve growth was still 

 poorly understood; before it was realized, 

 for instance, that nerve fibers cannot pene- 

 trate into the interior of a structureless fluid 

 in the manner of plants. It was assvimed 

 that remote tissues, by virtue of their electric 

 charges or of specific chemical emanations, 

 could "attract" nerve growth from a distance. 

 This assumption implies (1) that the sup- 

 posed gradients be steady and durable, and 

 undisturbed by any activities within the in- 

 tervening distance, and (2) that the nerve 

 tip has means not only for perceiving the 

 required minute differentials of potential or 

 concentration, but also for translating them 

 into corresponding steering actions. Neither 

 these premises nor the basic thesis of distance 

 attraction has ever been critically demon- 

 strated. On the contrary, overwhelming evi- 

 dence has accumulated over the years to dis- 

 prove them. 



Repeated attempts to obtain directed nerve 

 growth along the stream lines of an electric 

 field have remained unsuccessful. Indeed the 

 very possibility of an electric guidance is 

 ruled out by the fact that nerve growth often 

 proceeds simultaneously in diametrically op- 

 posite directions (e.g., the ascending and 

 descending branches of dorsal root fibers; 

 recurrent fibers in nerve regeneration; re- 



