In the developing mammalian brain, neurons are highly migratory, and their final destinations are often far from their sites of origin in the proliferative zones. Their migration pathways have been extensively mapped in laboratory animals, but as Letinic and Rakic report in Nature Neuroscience, it might not always be appropriate to extrapolate these findings to humans. The authors have identified a migration pathway, from the telencephalon to the dorsal thalamus (DT), that seems to be unique to the human brain, and that might have contributed to the expansion of certain brain regions during evolution.

The DT arises from the diencephalon, yet in the human brain it undergoes considerable growth after proliferation has ceased in this region, indicating that cells are being imported from elsewhere. Previous studies in fixed tissue provided evidence for a migratory stream between the telencephalic ganglionic eminence (GE) and the DT, but nobody had seen it in action. Letinic and Rakic labelled GE cells with the lipophilic marker DiI and tracked their migration in brain slices from human fetuses. They showed that cells from the medial portion of the GE migrate to the DT. The origin of the migrating cells was further confirmed by immunohistochemistry; they produce the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and the DLX1 and DLX2 homeodomain proteins, all of which are characteristic of GE-derived cells.

This migration pathway has not been identified in any other mammals, even in primates that are closely related to humans, such as the macaque monkey. So, what is different about the human brain in this region? In explant cultures, Letinic and Rakic showed that human DT tissue is attractive to human GE cells. Mouse DT tissue, on the other hand, neither attracts nor repels mouse GE cells, but they are repelled by the subthalamus, which lies between the GE and the DT. By contrast, human subthalamic tissue has no effect on GE cell migration in vitro, so it presumably presents no barrier to migration in vivo. On the basis of these experiments alone, it is not clear whether it is the adhesive properties of the GE cells or of the GE–DT migratory pathway that have changed in the human brain. This issue might be resolved by cross-species grafting experiments, and by identifying the molecular cues that mediate the attractive and repulsive activities.

During evolution, the acquisition of higher cognitive ability in humans has been attributed to enlargement of the association areas of the cortex and the thalamic nuclei that connect to these regions. This study shows that the proliferative zone of the developing human telencephalon not only contributes more cells to the cortex, but also provides a source of GABA-producing cells that migrate the DT. This migratory link between the telencephalon and the thalamus might provide the key to understanding how these regions could have evolved in tandem.