Interneurons are critical to higher cortical processing and conversely malfunction of these cells is clinically implicated as a cause of epilepsy, chorea and dyskinesia. Recent work has determined that cortical interneurons are largely or completely derived from the subpallial portion of the telencephalon. Using a novel transplantation approach, we have recently fate mapped the caudal versus the medial ganglionic eminences of the E13.5 mouse brain. While we find that both these regions are sources of cortical interneurons, the laminar distribution, tiling and morphology of cells originating from these 2 eminences are distinct. We have begun to characterize interneurons originating from these 2 eminences on the basis of their evoked firing pattern, immunological markers and morphology. In particular we wish to assess whether the interneurons that are derived from these structures changes as development progresses. In addition, we propose to extend this study by genetically fate mapping whether specific developmental expressed bHLH and homeodomain transcription factors are expressed in progenitors that give rise to specific subclasses of cortical interneurons. This proposal will therefore provide the first comprehensive analysis of the developmental origins of cortical interneuron diversity.
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