Genome-wide analyses of human perisylvian cerebral cortical patterning
Genome-wide analyses of human perisylvian cerebral cortical patterning
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DOI：
10.1073/pnas.0706128104
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发表时间：
2007-11-06
影响因子：
11.1
通讯作者：
Geschwind, D. H.
中科院分区：
文献类型：
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作者：
Abrahams, B. S.;Tentler, D.;Geschwind, D. H.
尽管额叶和后外侧裂周皮质在包括语言在内的人类认知专业化的许多方面都有着明确的作用，但人们对人类大脑中这些区域的发育模式知之甚少。我们对人类在妊娠中期的大脑模式进行了全基因组分析，这是皮质区域化的关键时期。共有345个基因被鉴定为在上级颞回（STG）和其余大脑皮层之间差异表达。代表转录因子的基因本体类别在STG中富集，而细胞粘附和细胞外基质分子在其他皮质区域中富集。进行定量IRT-PCR或原位杂交以验证32个基因的子集中的差异表达，其中大部分被证实。LIM结构域结合1（LDB 1），我们显示是在STG中富集的，是最近确定的LIM结构域仅4（LM 04）的相互作用物，LIM结构域仅4（LM 04）是已知参与发育中的人脑中的侧裂周区域的不对称图案化的基因。原钙粘素17（PCDH 17），神经细胞粘附分子，高度富集在人类前额叶皮层的局灶性区域。接触素相关蛋白样2（CNTNAP 2），其中突变已知会导致自闭症，癫痫和语言延迟，显示出在人类中未观察到的前富集皮质表达的显着模式。这些数据突出了人脑表达分析的重要性和跨物种基因表达比较的实用性。这里确定的基因为理解人类认知专业化的分子方面以及破坏它们的疾病提供了基础。
Despite the well established role of the frontal and posterior perisylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in the human brain. We performed a genome-wide analysis of human cerebral patterning during midgestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed between superior temporal gyrus (STG) and the remaining cerebral cortex. Gene ontology categories representing transcription factors were enriched in STG, whereas cell-adhesion and extracellular matrix molecules were enriched in the other cortical regions. Quantitative IRT-PCR or in situ hybridization was performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain-binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LM04), a gene known to be involved in the asymmetric pattering of the perisylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin associated protein-like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy, and language delay, showed a remarkable pattern of anterior-enriched cortical expression in human that was not observed in mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and the disorders that disrupt them.