VII 



INTERNAL FACTORS 64I 



tional area decreases with age (Van Stone, 1955) and this may underlie the normal age- 

 decHne in power of regeneration (Singer, 1952). A similar change may explain why the 

 phylogenetic trend towards increased body-size involves a concomitant decline in regener- 

 ative power. 



Denervation of the stump of an amputated limb results in regression of the stump 

 (Schotte and Butler, 1941 ; Thornton and Kraemer, 1951). This is perhaps a rever- 

 sal of the growth-promoting and maintenance functions of intact nerve, though it 

 is quite distinct from the slower process of atrophy which follows denervation of 

 intact limbs (Schotte and Butler, 1941), and normally requires the additional stim- 

 ulus of wound-factors. It is also different from normal dedifferentiation (Schotte 

 and Butler, 1944). The injury need not be an amputation (Thornton, 1953); if 

 it is a crush-injury, not at the end of the denervated limb, then regression proceeds 

 both ways from the crushed region. Denervated barbels of the catfish regress 

 without amputation (Kamrin and Singer, 1955). Regression halts as tissues are 

 reinnervated and a blastema forms at a terminal surface of regression. Non-ter- 

 minal regression however is not made good by regeneration (Thornton, I.e.) so 

 that again factors other than neural also are involved. Regression can be halted by 

 grafting an established blastema (Schotte and Butler, 1941, 1944), too. 



If a limb is denervated before amputation, regression is smaller (Karczmar, 

 1946) and regeneration is less retarded (Needham, 1946a) than when denervation 

 is simultaneous with amputation. Conversely both are enhanced if denervation is 

 performed a few days after amputation. The P-phase begins as soon as the tip of 

 the stump is innervated. Regression due to other causes (pp. 624, 627) is halted 

 by nerve-regeneration. 



Innervation is not necessary for the early stages of wound-healing ( Janda, 1 930 ; 

 Gorelova, 1954; Roguski, 1954) but it appears to be essential for the cell-move- 

 ments of blastema-formation (Schotte and Butler, 1941, 1944, 1949; Thornton, 

 1954) in both epidermis and mesodermal tissues. In Planarians (Hyman, 1951; 

 p. 188) and Annelids (Stone, 1933), neoblasts migrate into the blastema along- 

 side the ventral nerve cords. A regenerating nerve promotes the migration of its 

 own Schwann-cells (Abercrombie et al., 1949). Grafts of pieces of the central 

 nervous system of Amphibia induce cell-migrations in the vicinity (Overton, 

 1950). If the young blastema is denervated it regresses once more. 



Cell-migration and cell-proliferation are intimately related (Medawar, 1940) 

 and the action of the peripheral nerve is probably primarily on the latter (Singer 

 and Craven, 1948; Butler and Schotte, 1949). Denervation during the early stages 

 of growth of the blastema (Fig. 2, p. 605) reduces the number of mitoses and 

 retards or halts growth. As the interval between amputation and denervation is 

 increased progressively the response of the regenerate changes from regression, 

 through mere arrest and then decreasing retardation, to indifference; the later 

 stages, of cell-hypertrophy and differentiation, appear to be virtually independent 

 of innervation. No doubt it is significant that the kinetosome-system of ciliate 

 Protozoa, and the corresponding structures in flagellates, are frequently connected 

 to the centrosome and so, like the nervous system of Metazoa, control mitosis. 

 Cell-division is a motor function with considerable similarity to muscular con- 

 traction (Brachet, 1950, p. 184) and other motor functions, so that its control by 



Literature p. 641) 



