Investigating gradients of gene expression involved in early human cortical development
Investigating gradients of gene expression involved in early human cortical development
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DOI：
10.1111/j.1469-7580.2010.01259.x
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发表时间：
2010-10-01
影响因子：
2.4
通讯作者：
Bayatti, Nadhim
中科院分区：
文献类型：
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作者：
Ip, Bui K.;Wappler, Ilka;Bayatti, Nadhim
尽管发育过程中的大脑损伤可能导致区域身份的实质性重组，但新皮质划分为功能区域（皮质图）的情况在个体之间差异不大。我们正在研究人脑中的皮质图是如何建立的，这是理解这种可塑性的第一步。先前关于啮齿动物发育的研究已经确定了在新皮质中以梯度表达的某些转录因子（例如 Pax6、Emx2），这些转录因子似乎控制细胞粘附分子的区域表达和区域特异性丘脑皮质传入投射的组织。尽管机制可能是共享的，但人类新皮质是由不同且更复杂的局部区域特征组成的。使用受孕后 8 至 12.5 周的人类胎儿脑组织的 Affymetrix 基因芯片 [PCW，相当于卡内基阶段 (CS) 23，到胎儿阶段 (F) 4]，人类材料从 MRC-Wellcome Trust 人类发育生物学资源 (http://www.hdbr.org) 获得，我们鉴定了许多沿新皮质前后轴表现出梯度的基因。与前部相比，后部上调的基因探针组包括 EMX2、COUPTFI 和 FGF 受体 3，前部上调的基因探针组包括细胞粘附分子，如钙粘蛋白和原钙粘蛋白，以及潜在的运动皮层标记和额叶标记（例如 CNTNAP2、PCDH17、ROBO1 和 CTIP2）。使用实时 PCR 对这些基因的子集的分级表达进行了确认。此外，我们利用从前部或后部衍生的发育中的人类新皮质解剖的组织建立了解离细胞培养模型，该模型在培养中至少72小时表现出相似的这些基因的表达梯度。
The division of the neocortex into functional areas (the cortical map) differs little between individuals, although brain lesions in development can lead to substantial re-organization of regional identity. We are studying how the cortical map is established in the human brain as a first step towards understanding this plasticity. Previous work on rodent development has identified certain transcription factors (e.g. Pax6, Emx2) expressed in gradients across the neocortex that appear to control regional expression of cell adhesion molecules and organization of area-specific thalamocortical afferent projections. Although mechanisms may be shared, the human neocortex is composed of different and more complex local area identities. Using Affymetrix gene chips of human foetal brain tissue from 8 to 12.5 post-conceptional weeks [PCW, equivalent to Carnegie stage (CS) 23, to Foetal stage (F) 4], human material obtained from the MRC-Wellcome Trust Human Developmental Biology Resource (http://www.hdbr.org), we have identified a number of genes that exhibit gradients along the anterior-posterior axis of the neocortex. Gene probe sets that were found to be upregulated posteriorally compared to anteriorally, included EMX2, COUPTFI and FGF receptor 3, and those upregulated anteriorally included cell adhesion molecules such as cadherins and protocadherins, as well as potential motor cortex markers and frontal markers (e.g. CNTNAP2, PCDH17, ROBO1, and CTIP2). Confirmation of graded expression for a subset of these genes was carried out using real-time PCR. Furthermore, we have established a dissociation cell culture model utilizing tissue dissected from anteriorally or posteriorally derived developing human neocortex that exhibits similar gradients of expression of these genes for at least 72 h in culture.