Microtubules and motor proteins support zebrafish neuronal migration by directing cargo

Abstract

Neuronal migration during development is necessary to form an ordered and functional brain. Postmitotic neurons require microtubules and dynein to move, but the mechanisms by which they contribute to migration are not fully characterized. Using tegmental hindbrain nuclei neurons in zebrafish embryos together with subcellular imaging, optogenetics, and photopharmacology, we show that, in vivo, the centrosome’s position relative to the nucleus is not linked to greatest motility in this cell type. Nevertheless, microtubules, dynein, and kinesin-1 are essential for migration, and we find that interference with endosome formation or the Golgi apparatus impairs migration to a similar extent as disrupting microtubules. In addition, an imbalance in the traffic of the model cargo Cadherin-2 also reduces neuronal migration. These results lead us to propose that microtubules act as cargo carriers to control spatiotemporal protein distribution, which in turn controls motility. This adds crucial insights into the variety of ways that microtubules can support successful neuronal migration in vivo.