Fine Structural Changes in Neurons and Nerve Fibers Associated With Colchicine Inhibition of Nerve Fiber Formation in Vitro

Neurotubules appear to be homologous to the cytoplasmic microtubules of other cell types in both their morphological (Gonatas and Robbins, 1964) and chemical (Weisenberg et al., 1968) characteristics. There is a large body of evidence indicating that microtubules have an important role in the development and maintenance of asymmetric form in cells and cell processes (reviewed by Tilney, 1968) . For this reason it has been proposed that microtubules take part in the development and maintenance of the elongate form of neurites (Porter, 1966) . There is some experimental evidence for this proposition, based on the effects of colchicine, which disrupts microtubules in vivo and in vitro (Weisenberg, 1972) through its specific binding to the protein subunit of that organelle (Taylor, 1965 ; Borisy and Taylor, 1967 a, b ; Shelanski and Taylor, 1967, 1968) . It has been demonstrated that colchicine disrupts the microtubules of spinal neurons (Wisniewski et al., 1968), inhibits the sprouting of severed axons of the sciatic nerve (Hoffman, 1952), and both inhibits neurite outgrowth and causes retraction of neurites in monolayer cultures of chick dorsal-root ganglia (Daniels, 1968 ; Yamada et al., 1970) . Daniels (1972) demonstrated that these effects of colchicine take place within 3-6 h of treatment with a low concentration of the alkaloid, 0 .05 μg/ml, and are reversible under these same conditions . The present report is concerned with changes in density of microtubules and neurofilaments in the neurons and neurites of these monolayer cultures during colchicine inhibition of neurite elongation and after reversal of this inhibition .