Diverse subtypes of GABAergic interneurons populate the mammalian neocortex. Using inducible in vivo genetic fate mapping strategies, we have recently shown that the medial and caudal ganglionic eminence (MGE and CGE) give rise to distinct subtypes of cortical interneurons, based on their morphologies, molecular expression profiles and intrinsic firing properties. Compared to the MGE-derived interneuron lineages, which are specified by the transcriptional cascade of Nkx2-1 - Lhx6 - Sox6, little is known about the CGE-derived interneurons. We have performed a microarray analysis of CGE-derived interneuron enriched genes, and are presently characterizing candidate transcription factors that specify CGE interneuron properties.

The six-layered mammalian neocortex is formed through the sequential addition of neurons entering the cortical plate in an inside-out manner. Newly born pyramidal neurons cross the intermediate zone as they transit from the proliferative zone to the cortical plate. During this process these migrating precursors are known to transiently adopt a multipolar morphology. At this phase, migrating cells detach from radial glia and are able to move tangentially and initiate the extension of their axon. Subsequently these cells revert to a bipolar morphology, reattach to radial glia and proceed onwards into the cortical plate. Despite the fact that these highly dynamic steps seem critical to pyramidal cell layer development, little is known concerning the genetic programs that direct these events. We observe that the forkhead box transcription factor FoxG1 is transiently down- regulated at the entrance of multipolar cell phase and re-expressed as they proceed onward into the cortical plate. By combining gain- and loss-of-function strategies, we demonstrate that FoxG1 plays a pivotal role in coordinating the transition into and out of the multipolar cell phase. Importantly, failure of FoxG1 re-initiation during the multipolar cell phase will prevent pyramidal neuron precursors from entering the cortical plate. Moreover, we demonstrate that in a FoxG1 dependent manner multiple signaling pathways contribute to these events. We conclude that the precise genetic control of the multipolar cell phase is essential for building a functional cortical network and disruption of this process may be the underlying etiology of multiple neurodevelopmental disorders.