Xu Qing, Cobos Inma, De La Cruz Estanislao, Rubenstein John L, Anderson Stewart A
Department of Psychiatry, Weill Medical College of Cornell University, New York, New York 10021, USA.
J Neurosci. 2004 Mar 17;24(11):2612-22. doi: 10.1523/JNEUROSCI.5667-03.2004.
Cerebral cortical functions are conducted by two general classes of neurons: glutamatergic projection neurons and GABAergic interneurons. Distinct interneuron subtypes serve distinct roles in modulating cortical activity and can be differentially affected in cortical diseases, but little is known about the mechanisms for generating their diversity. Recent evidence suggests that many cortical interneurons originate within the subcortical telencephalon and then migrate tangentially into the overlying cortex. To test the hypothesis that distinct interneuron subtypes are derived from distinct telencephalic subdivisions, we have used an in vitro assay to assess the developmental potential of subregions of the telencephalic proliferative zone (PZ) to give rise to neurochemically defined interneuron subgroups. PZ cells from GFP+ donor mouse embryos were transplanted onto neonatal cortical feeder cells and assessed for their ability to generate specific interneuron subtypes. Our results suggest that the parvalbumin- and the somatostatin-expressing interneuron subgroups originate primarily within the medial ganglionic eminence (MGE) of the subcortical telencephalon, whereas the calretinin-expressing interneurons appear to derive mainly from the caudal ganglionic eminence (CGE). These results are supported by findings from primary cultures of cortex from Nkx2.1 mutants, in which normal MGE fails to form but in which the CGE is less affected. In these cultures, parvalbumin- and somatostatin-expressing cells are absent, although calretinin-expressing interneurons are present. Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures of Dlx1/2 mutants. By establishing spatial differences in the origins of interneuron subtypes, these studies lay the groundwork for elucidating the molecular bases for their distinct differentiation pathways.
谷氨酸能投射神经元和γ-氨基丁酸能中间神经元。不同的中间神经元亚型在调节皮质活动中发挥不同作用，并且在皮质疾病中可能受到不同影响，但对于产生其多样性的机制知之甚少。最近的证据表明，许多皮质中间神经元起源于皮质下的端脑，然后切向迁移到上方的皮质中。为了验证不同的中间神经元亚型源自不同的端脑亚区这一假设，我们使用了一种体外测定法来评估端脑增殖区（PZ）亚区产生神经化学定义的中间神经元亚组的发育潜力。将来自绿色荧光蛋白（GFP）阳性供体小鼠胚胎的PZ细胞移植到新生皮质饲养细胞上，并评估它们产生特定中间神经元亚型的能力。我们的结果表明，表达小白蛋白和生长抑素的中间神经元亚组主要起源于皮质下端脑的内侧神经节隆起（MGE），而表达钙视网膜蛋白的中间神经元似乎主要源自尾侧神经节隆起（CGE）。来自Nkx2.1突变体皮质原代培养物的研究结果支持了这些结果，在该突变体中正常的MGE无法形成，但CGE受影响较小。在这些培养物中，不存在表达小白蛋白和生长抑素的细胞，尽管存在表达钙视网膜蛋白的中间神经元。有趣的是，在Dlx1/2突变体的皮质培养物中，表达钙视网膜蛋白的双极中间神经元几乎不存在。通过确定中间神经元亚型起源的空间差异，这些研究为阐明其不同分化途径的分子基础奠定了基础。
