Fine structures of the mammalian brain are formed by neuronal migration during
development. Newborn neurons migrate long distances from the germinal zone to individual
sites of function by squeezing their largest cargo, the nucleus, through the crowded
neural tissue. Nuclear translocation is thought to be orchestrated by microtubules, actin,
and their associated motor proteins, dynein and myosin. However, where and how the
cytoskeletal forces are converted to actual nuclear movement remains unclear. Using
high-resolution confocal imaging of live migrating neurons, we demonstrated that
microtubule-dependent forces are directly applied to the nucleus via the linker of
nucleoskeleton and cytoskeleton complex, and that they induce dynamic nuclear movement,
including translocation, rotation, and local peaking. Microtubules bind to small points on
the nuclear envelope via the minus- and plus-oriented motor proteins, dynein and
kinesin-1, and generate a point force independent of the actin-dependent force. Dynamic
binding of microtubule motors might cause a continuously changing net force vector acting
on the nucleus and results in a stochastic and inconsistent movement of the nucleus, which
are seen in crowded neural tissues.