Layer specification of transplanted interneurons in developing mouse neocortex.

The six-layered neocortex is composed of excitatory projection neurons and inhibitory interneurons. Recent studies have established separate embryological origins for these two cellular populations. However, it remains uncertain how interneurons arising from the subcortical ganglionic eminences are able to participate in the orderly stratification of the cortical layers. A related question concerns whether or not early and late interneuron progenitors have equivalent developmental potentials. To address these issues, we performed transplantation experiments to test the fates of early-versus late-born interneuron populations using cells labeled with a genetic marker. Our results indicate that transplanted interneurons from the medial ganglionic eminence give rise to specific layers of the neocortex in an inside-out order. To test the potency of interneurons born at different ages, heterochronic transplantations were also performed. Both early- and late-born progenitors were able to switch their fates in the new environment, and, similar to projection neurons, fate-switching was dependent on progenitor receptivity to environmental cues during their last round of cell division. Our data also demonstrate, for the first time, that interneuron-layering cues are present within the medial ganglionic eminence, suggesting that, before the commencement of long-distance tangential migration, interneurons are already specified with respect to their future layer addresses. So, although the generation of diverse neuronal phenotypes in separate locations is an effective strategy to pursue separate developmental programs, our results indicate that excitatory and inhibitory neurons share similar mechanisms for integrating sequentially born neurons from two places into a single layered structure.