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Application of microarray, laser capture and transgenic technologies to the study of neural diversity.

机译：微阵列，激光捕获和转基因技术在神经多样性研究中的应用。

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摘要

A major quest in modern neurobiology is to understand how the brain controls behavior. To this end, the convergence of two traditionally separate fields, systems neuroscience and molecular neuroscience, is required. The delineation of brain regions responsible for different behaviors, and in particular, their underlying neural circuits should be accompanied by the appreciation of the molecules that compose such circuits.; I have taken two approaches toward unraveling the molecular signatures of specific neural structures. First, I conducted microarray-based RNA expression analyses to search, in a large scale and with no a priori constraints, for differentially expressed gene products in several brain regions, including the amygdala, cerebellum, hippocampus, olfactory bulb and periaqueductal gray. Interestingly, only 0.3% of the genes characterized to date showed restricted expression in distinct brain areas. Further characterization by in situ hybridization was performed for genes enriched in the amygdala, a structure that modulates emotional behavior. Remarkably, this revealed that most region-specific genes possessed expression domains whose limits respected subnuclear boundaries defined by classical cytoarchitectonic criteria. These analyses were not only informative about the molecular composition of distinct brain areas, but also provided tools to genetically dissect the role of different brain nuclei in specific behaviors.; Second, I have used a genetic strategy to label all cellular derivatives of neural crest precursor cells expressing a particular gene, Ngn2 . Such lineage tracing study uncovered a segregated cellular subpopulation in the developing peripheral nervous system, which was strongly biased for the generation of sensory rather than autonomic neurons. Despite this fate bias, Ngn2-derived cells in the dorsal root ganglion were equally likely to give rise to neurons or glia. This suggests that some neural crest cells become restricted to sensory or autonomic sublineages before becoming committed to neuronal or glial fates. In general, visualization of the behavior of neural progenitors during the formation of the nervous system may further our understanding of the generation of specific neuronal subtypes and, eventually, neuronal connections that shape the functioning brain.
机译：现代神经生物学的主要追求是了解大脑如何控制行为。为此，需要两个传统上分离的领域，即系统神经科学和分子神经科学的融合。划定负责不同行为的大脑区域，尤其是其潜在的神经回路，应伴随着对构成这种回路的分子的欣赏。我采取了两种方法来揭示特定神经结构的分子特征。首先，我进行了基于微阵列的RNA表达分析，在没有先验限制的情况下大规模搜索了多个大脑区域（包括杏仁核，小脑，海马，嗅球和导水管周围的灰色区域）中差异表达的基因产物。有趣的是，迄今为止只有0.3％的基因在不同的大脑区域显示出限制性表达。通过原位杂交对富含杏仁核的基因进行了进一步表征，杏仁核是一种调节情绪行为的结构。值得注意的是，这表明大多数区域特异性基因都具有表达域，其表达范围受经典细胞建筑学标准定义的亚核边界的限制。这些分析不仅为不同大脑区域的分子组成提供了信息，而且为遗传剖析不同脑核在特定行为中的作用提供了工具。其次，我使用了一种遗传策略来标记表达特定基因 Ngn2 的神经precursor前体细胞的所有细胞衍生物。此类谱系追踪研究发现发育中的周围神经系统中存在分离的细胞亚群，该亚群在感觉神经而不是自主神经元的产生上存在强烈偏见。尽管存在这种命运偏见，但背根神经节中 Ngn2 衍生的细胞同样有可能产生神经元或神经胶质。这表明一些神经c细胞在致力于神经元或神经胶质命运之前就已经局限于感觉或自主神经亚系。通常，在神经系统形成过程中对神经祖细胞行为的可视化可能会进一步使我们了解特定神经元亚型的产生，并最终了解形成功能性大脑的神经元连接。

著录项

  • 作者

    Zirlinger, Mariela.;

  • 作者单位

    California Institute of Technology.;

  • 授予单位 California Institute of Technology.;
  • 学科 Biology Neuroscience.; Biology Molecular.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 166 p.
  • 总页数 166
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;分子遗传学;
  • 关键词

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