Motor and Sensory Hyperplasia following Limb-Bud Transplantations in Chick Embryos

THE factors controlling growth and differentiation of the vertebrate nervous system have been extensively studied in amphibian embryos. The experimental T analysis revealed three main groups of factors: (i) patterns of local proliferation and differentiation, (2) mutual correlations between the different regions of the central nervous system, and (3) growth-controlling factors residing in the nonnervous peripheral structures, to be innervated (see reviews by Harrison, 1935, and Detwiler, 1936). The present report deals exclusively with the last-mentioned factors. For Amblystoma, Detwiler and others have shown that spinal ganglia react sensitively to a decrease or an increase of their peripheral fields. A reduction of their peripheral area (e.g., by the extirpation of a limb) results in a hypoplasia of approximately 50 per cent, whereas peripheral overloading (e.g., by implanting an additional limb) causes a hyperplasia up to 40 per cent. In both instances the spinal cord and, in particular, its motor area showed no reaction; its cell number was in no way changed by the changes in its peripheral fields. Diirken (1912) and May (1930, 1933), on the other hand, reported positive reactions of the spinal cord of the frog, following the same type of operations: a hypoplasia of the motor column after limb-bud extirpation, and its hyperplasia after implantation of an accessory limb. Results similar to the last mentioned were obtained on chick embryos. A marked hypoplasia of the lateral motor column, in addition to hypoplasia of the corresponding spinal ganglia, was found when wing buds were extirpated in chick embryos incubated 3 days (Shorey, 1909; Hamburger, I934). The difference in the reaction of the motor cells between Amblystoma, on the one hand, and the frog and chick, on the other, was attributed to the absence in the former forms, and the presence in the latter, of a distinct lateral motor horn (see Hamburger, 1934, p. 488). The mechanism through which the peripheral structures affect processes going on in the central nervous system is still obscure. Considering, for a moment, the reaction of the motor horn in the chick, the only clue we have found is in the following observations: (i) the spinal ganglion and the motor column of the same segment react independently of each other; and (2) the motor hypoplasia is proportional to the amount of loss of muscle tissue. Obviously, we are dealing neither with a growth stimulus transmitted through a reflex are nor with a mass reaction of the central nervous system, but with a localized, almost point-to-point, stimulation of a certain area of motor neuroblasts by their own endorgans (differentiating muscles). The tentative explanation was proposed that a growthcontrolling agent travels in centripetal direction along the pathfinder motor fibers which first reach the peripheral area. This agent would be produced in a quantity proportionate to the size of the peripheral area to be innervated and would control, in a quantitative way, either the mitotic activity or certain steps in the differentiation of the neuroblasts which lie in the neighborhood of the pathfinder neurons (Hamburger, I934). This investigation was supported by a grant from the Rockefeller Foundation. The author is greatly indebted to Mr. Eugene L. Keefe for his valuable assistance.