The microtubule cytoskeleton and the development of neuronal polarity.

The concept that axons and dendrites represent a fundamental polarization of the nerve cell has been borne out by numerous morphological, functional, and molecular studies. How does polarity arise during development? We and others have focused on the role of the microtubule cytoskeleton because microtubules (a) are essential components of axons and dendrites; (b) possess an inherent polarity at the molecular level; (c) are regulated by interactions with microtubule associated proteins (MAPs), some of which have polarized distributions in mature neurons. Here we review data on the initial acquisition of polarity as observed in neuronal culture and roles for microtubules and MAPs in this morphogenetic event. We present data clarifying some previously conflicting results on tau localization during the establishment of polarity and provide new evidence that phosphorylation of tau is spatially regulated during the development of polarity in culture. Elucidation of mechanisms locally regulating tau phosphorylation during normal neuronal development may provide clues to the significance of its abnormal phosphorylation in Alzheimer's disease.