With shorter neurites, wild-type interneuron precursors (top) migrate more easily than gangly Dlx1/2 mutants (bottom).


Neurons with overly long axons and dendrites can't migrate, report Inma Cobos, Ugo Borello, and John Rubenstein (University of California, San Francisco, CA).

Cortical interneurons migrate to their adult location in the cortex during embryogenesis. It has been known for some time that the transcription factors Dlx1 and Dlx2 control this migration, but just how they manage it was unclear.

Dlx1/2 are normally expressed at high levels in new interneurons and gradually reduce to low levels in postmigratory cells. Cobos et al. show that young interneuron precursors taken from mice lacking Dlx1/2 have much longer neurites (axons and dendrites) than their wild-type counterparts. The overly long neurites were associated with increased expression of several cytoskeleton regulatory genes.

The team showed that PAK3 kinase, one of these regulators, was expressed at almost undetectable levels in newborn and migrating wild-type precursor interneurons. Its expression rose to high levels once interneurons reached the cortex. Suppression of PAK3 with siRNA in the Dlx mutant interneuron precursors led to shorter neurites and partly restored migratory ability.

In addition to their migratory defects, Dlx mutant interneurons were also prone to apoptosis. The researchers are currently investigating other Dlx target genes to determine how, if at all, interneuron survival is linked to migration.


Cobos, I., et al.