Branching of sensory and sympathetic neurites in vitro is inhibited by treatment with taxol.

Branching of elongating neurites in vitro occurs by the division of a growth cone into 2 or more daughter neurites. An important initial step is a broadening of the growth cone with establishment of a quiescent central growth cone margin. Within the spreading growth cone, microtubules and associated neuritic components diverge and become oriented toward the lateral protrusive margins of the leading edge (Letourneau, 1983). We have found that a low concentration of the microtubule-stabilizing agent taxol severely reduces the incidence of growth cone branching by cultured sensory and sympathetic neurons from chick embryos. In the presence of taxol, neurites are broader and have more microtubules than normally. Divergence of microtubules entering the growth cone from the proximal neurite is reduced in the presence of taxol, and quiescence of the central growth cone margin is less frequent. We propose that a critical step in branching is the separation and spreading of the neurite cytoskeleton by tensions generated at the lateral margins of the edge of the growth cone. Because taxol increases neurite size and microtubule content without increasing protrusive activity to the same extent, tensions produced in the motile leading edge are insufficient to spread the microtubules and associated neuritic materials into separate arrays for nascent branches.