Hierarchical clustering of gene expression patterns in the Eomes + lineage of excitatory neurons during early neocortical development.
Hierarchical clustering of gene expression patterns in the Eomes + lineage of excitatory neurons during early neocortical development.
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DOI：
10.1186/1471-2202-13-90
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发表时间：
2012-08-01
期刊：
影响因子：
2.4
通讯作者：
Olson EC
中科院分区：
文献类型：
--
作者：
Cameron DA;Middleton FA;Chenn A;Olson EC
大脑皮层神经元在发育过程中的分化和迁移过程中表现出动态的基因表达模式。为了鉴定由兴奋性皮质神经元的Eomes +（Tbr 2）谱系选择性表达的基因，将来自Tg（Eomes：：eGFP）Gsat胚胎的GFP表达细胞分离至> 99%纯度并进行分析。我们报告的识别，验证和空间分组的基因选择性表达的Eomes +皮质兴奋性神经元谱系在早期皮质发育。在这些神经元中，与神经元前体的参考群体相比，475个基因表达≥ 3倍，534个基因表达≤ 3倍。在上调基因中，Genepaint原位杂交数据库中有328个基因，其中317个（97%）经验证具有与分化兴奋性神经元谱系一致的空间表达模式。一种新的方法，定量原位杂交模式（QISP）在整个大脑壁的开发，允许层次聚类的基因到假定的共调节组。44个候选基因被鉴定为在中间前体细胞中显示空间表达，49个候选基因在多极神经元中显示空间表达，而其余224个基因在发育中的皮质板中达到峰值表达。这种对分化的兴奋性神经元的分析揭示了37种转录因子、许多趋化性信号分子（包括脑信号蛋白、Netrin和Slit信号通路）的表达模式，以及非经典神经递质信号传导和葡萄糖代谢机制变化的意外证据。超过一半的317个基因与神经元疾病相关，使这些发现成为研究神经发育和疾病的宝贵资源。
Cortical neurons display dynamic patterns of gene expression during the coincident processes of differentiation and migration through the developing cerebrum. To identify genes selectively expressed by the Eomes + (Tbr2) lineage of excitatory cortical neurons, GFP-expressing cells from Tg(Eomes::eGFP) Gsat embryos were isolated to > 99% purity and profiled. We report the identification, validation and spatial grouping of genes selectively expressed within the Eomes + cortical excitatory neuron lineage during early cortical development. In these neurons 475 genes were expressed ≥ 3-fold, and 534 genes ≤ 3-fold, compared to the reference population of neuronal precursors. Of the up-regulated genes, 328 were represented at the Genepaint in situ hybridization database and 317 (97%) were validated as having spatial expression patterns consistent with the lineage of differentiating excitatory neurons. A novel approach for quantifying in situ hybridization patterns (QISP) across the cerebral wall was developed that allowed the hierarchical clustering of genes into putative co-regulated groups. Forty four candidate genes were identified that show spatial expression with Intermediate Precursor Cells, 49 candidate genes show spatial expression with Multipolar Neurons, while the remaining 224 genes achieved peak expression in the developing cortical plate. This analysis of differentiating excitatory neurons revealed the expression patterns of 37 transcription factors, many chemotropic signaling molecules (including the Semaphorin, Netrin and Slit signaling pathways), and unexpected evidence for non-canonical neurotransmitter signaling and changes in mechanisms of glucose metabolism. Over half of the 317 identified genes are associated with neuronal disease making these findings a valuable resource for studies of neurological development and disease.
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