How cortical interneurons find their address

It is not known how cortical interneurons find their specific layer-address. It was long debated if their fate is specified before they reach the neocortex or if they are guided by local information within the cortical layers (Marin O. & Rubenstein J. L., A long remarkable jorney: tangential migration in the telencephalon. Nature Review Neuroscience 2, 780-790, 2001; Nadarajah B. & Parnavelas J. G., Modes of neural migration in the developing cerebral cortex. Nature Review Neuroscience 3, 423-432, 2002). We have known that the cortical ventricular zone is a source of patterning signals for interneurons (Nadarajah B. et al., Ventricle directed migration in the developing cerebral cortex. Nature Neuroscience 5, 218-228, 2002) but now compelling new insights give us a more complex view of the initial part of this complex process.

The inhibitory GABA cells of the neocortex, called interneurons, originate in subcortical proliferative zones named the ganglionic eminences. They migrate from this zone in a tangential stream. Little is known about how these cells navigate in the cortical layer, but two studies give insights to the possible mechanisms. The first study (Valcanis H. & Tan S. S., Layer specification of transplanted interneurons in developing mouse neocortex. Journal of Neuroscience 23, 5113-5122, 2003) showed that in the mouse neocortex, interneurons populated the layers in an inside-out sequence, mirroring the order of placement of projections neurons. Apparently, their final destination is determined at the start of their journey, but this is not necessarily set in stone. For example, when the authors transplanted early-born interneuron progenitors into an older brain, these cells tended to adopt an abnormally superficial position. Progenitors that divided within the cortex were more prone to re-specification than post-mitotic progenitors. This indicated that the cells acquire some positional information from their immediate environment during their final phase of division.

In the second study (Stumm R. K. et al. CXCR4 regulates interneuron migration in the developing neocortex, Journal of Neuroscience 23, 5123-5130, 2003) the authors identified a signal that might be responsible for guiding some interneurons to their final destination. They found that the late-born interneurons that colonize the superficial layer express CXC chemokine receptor 4 (CXCR4) and a receptor for stromal cell-derived factor-1 (SDF-1). SDF-1 is expressed in the outermost layer of the developing cortex and it seems to attract CXCR4-expressing interneurons.

These findings indicate that the fate of cortical interneurons is partially specified before they reach the cortex, although a subset of cells might also pick up environmental information within the cortical layers.

Linda Faye Lehman & Giuseppe Perrella

BM&L-September 2003