Slowdown of microtubule retrograde flow enables axon and dendrite development and maintenance

Distinct microtubule arrays form in axons and dendrites defining their functions in neurons. These arrays are thought to develop through separate processes. Here we challenge this view by showing that axons and dendrites develop by a unifying process: slowdown of microtubule retrograde flow (MT-RF), a recently discovered mechanism of microtubule dynamics. By integrating quantitative data of microtubule dynamics and distributions into a newly developed biophysical model of microtubules across developmental stages, we uncover that MT-RF interacts with microtubule stability and nucleation. Without MT-RF slowdown, this interaction suppresses development and maintenance of axonal and dendritic microtubule arrays. In axons, MT-RF slowdown enables microtubules to reach the tip, even at long distances, supporting axon growth. In dendrites, late MT-RF slowdown facilitates an efficient increase in stable microtubules. Thus, our data-integrated model reveals MT-RF slowdown as central for the development of distinct neuronal compartments, providing a unifying mechanism for microtubule-related physiology.