Microtubule stabilization specifies initial neuronal polarization

TLDR

Axon formation is the initial step in establishing neuronal polarity. The study investigates how microtubule dynamics influence neuronal polarization in cultured hippocampal neurons. The authors used cultured hippocampal neurons to assess microtubule dynamics during polarization. They found that local microtubule stabilization in a single neurite precedes and directs axon formation, while altering microtubule dynamics—via nocodazole, taxol, or photoactivatable taxol—can suppress dendrite development or induce multiple axons, demonstrating that microtubule stability is a key signal for neuronal polarization.

Abstract

Axon formation is the initial step in establishing neuronal polarity. We examine here the role of microtubule dynamics in neuronal polarization using hippocampal neurons in culture. We see increased microtubule stability along the shaft in a single neurite before axon formation and in the axon of morphologically polarized cells. Loss of polarity or formation of multiple axons after manipulation of neuronal polarity regulators, synapses of amphids defective (SAD) kinases, and glycogen synthase kinase-3β correlates with characteristic changes in microtubule turnover. Consistently, changing the microtubule dynamics is sufficient to alter neuronal polarization. Application of low doses of the microtubule-destabilizing drug nocodazole selectively reduces the formation of future dendrites. Conversely, low doses of the microtubule-stabilizing drug taxol shift polymerizing microtubules from neurite shafts to process tips and lead to the formation of multiple axons. Finally, local stabilization of microtubules using a photoactivatable analogue of taxol induces axon formation from the activated area. Thus, local microtubule stabilization in one neurite is a physiological signal specifying neuronal polarization.