Regional and Genetic Diversity of Cortical Interneurons

项目概述：中间神经元对高级皮层处理至关重要，相反，这些细胞的功能障碍在临床上被认为是癫痫、舞蹈病和运动障碍的原因。最近的研究表明，皮层中间神经元大部分或全部来自端脑的苍白下部分。使用一种新颖的移植方法，我们最近绘制了E13.5小鼠大脑的尾侧和内侧神经节突起的命运图。虽然我们发现这两个区域都是皮层中间神经元的来源，但起源于这两个突出的细胞的层流分布、平铺和形态是不同的。我们已经开始根据它们的激发模式、免疫标记和形态来描述起源于这两个突起的中间神经元。特别是，我们希望评估来自这些结构的中间神经元是否随着发育的进展而变化。此外，我们建议通过基因命运定位来扩展这项研究，以确定特定发育表达的bHLH和同源结构域转录因子是否在产生特定皮层中间神经元亚类的祖细胞中表达。因此，这一建议将首次全面分析皮层中间神经元多样性的发育起源。

DESCRIPTION (provided by applicant): Project Summary: 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.