Nucleus demonstrates its independence


Japanese researchers unravel how cells move to form the brain


A RIKEN-led research team has shown that the nuclei of migrating nerve cells in the mouse brain move independently of the centrosomes, the organelles previously thought to pull them along. The work is important because disruption to nerve-cell migration during brain development, can impact the positioning and integration of cells. This can lead to neurological disorders, and has been implicated in conditions such as epilepsy, schizophrenia and bipolar disease.

Nerve cells or neurons are generated on the brain’s inner surface and migrate outwards to where they operate. Although neural migration is most evident during brain development, it continues throughout the animal’s adult life.

Neurons have long, thin projections called ‘processes’ extending from their cell bodies. During migration, a process extends in the direction of movement and the cell body with its organelles, of which the nucleus is the largest, then moves down that leading process.

The centrosome is the main organizing center for microtubules—strings of structural proteins, bundles of which form the dynamic skeleton in the cell. In many previous studies, researchers observed that the centrosome was nearly always positioned ahead of the nucleus during migration. It was thus thought that the nucleus was connected via microtubules through the centrosome to the leading process and was thereby dragged along.

Now, in a paper published recently in the Proceedings of the National Academy of Sciences (1), researchers from Kyoto University and the RIKEN Brain Science Institute in Wako show otherwise. Using time-lapse photography under a confocal microscope, they observed the movement of stained mouse neurons during migration. The nuclei exhibited a jumping motion—an alternating fast and slow movement—at times moving ahead of the centrosome.

When the researchers stained for bundles of stable and dynamic microtubules, they found the nucleus was connected to the leading process directly (Fig. 1); there was no intervening link to the centrosome, which is separately bound to the leading process. Stable microtubules, in particular, appear to be critical to nuclear movement, which is disrupted by the formation of too many or too few of them. The researchers also found that inhibiting LIS1, the product of a gene associated with a neural migration disorder, specifically affects nuclear movement, but not that of the centrosome.

“We now want to uncover the complete mechanism of nuclear and centrosomal movement,” says the project coordinator, Mineko Kengaku of the Brain Science Institute.

Reference

1. Umeshima, H., Hirano, T. & Kengaku, M. Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons. Proceedings of the National Academy of Sciences USA 104, 16182–16187 (2007).