TRANSPORT OF DENDRITIC MICROTUBULES ESTABLISHES THEIR NONUNIFORM POLARITY ORIENTATION

The immature processes that give rise to both axons and dendrites cont ain microtubules (MTs) that are uniformly oriented with their plus-end s distal to the cell body, and this pattern is preserved in the develo ping axon. In contrast, developing dendrites gradually acquire nonunif orm MT polarity orientation due to the addition of a subpopulation of oppositely oriented MTs (Baas, P. W., M. M. Black, and G. A. Banker. 1 989. J. Cell Biol. 109:3085-3094). In theory, these minus-end-distal M Ts could be locally nucleated and assembled within the dendrite itself , or could be transported into the dendrite after their nucleation wit hin the cell body. To distinguish between these possibilities, we expo sed cultured hippocampal neurons to nanomolar levels of vinblastine af ter one of the immature processes had developed into the axon but befo re the others had become dendrites. At these levels, vinblastine acts as a kinetic stabilizer of MTs, inhibiting further assembly while not substantially depolymerizing existing MTs. This treatment did not abol ish dendritic differentiation, which occurred in timely fashion over t he next two to three days. The resulting dendrites were flatter and sh orter than controls, but were identifiable by their ultrastructure, ch emical composition, and thickened tapering morphology. The growth of t hese dendrites was accompanied by a diminution of MTs from the cell bo dy, indicating a net transfer of MTs from one compartment into the oth er. During this time, minus-end-distal microtubules arose in the exper imental dendrites, indicating that new MT assembly is not required for the acquisition of nonuniform MT polarity orientation in the dendrite . Minus-end-distal microtubules predominated in the more proximal regi on of experimental dendrites, indicating that most of the MTs at this stage of development are transported into the dendrite with their minu s-ends leading. These observations indicate that transport of MTs from the cell body is an essential feature of dendritic development, and t hat this transport establishes the nonuniform polarity orientation of MTs in the dendrite.