Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia
Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia
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DOI：
10.1073/pnas.1218510110
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发表时间：
2013-02-26
影响因子：
11.1
通讯作者：
Molnar, Zoltan
中科院分区：
文献类型：
--
作者：
Hoerder-Suabedissen, Anna;Oeschger, Franziska M.;Molnar, Zoltan
亚板区是发育中的大脑皮层的高度动态的短暂部分，其中包含一些最早产生的神经元和大脑皮层的第一个功能性突触。亚板细胞在丘脑皮质连接的早期建立和成熟以及感觉区抑制性皮质回路的发育中具有重要功能。到目前为止，还没有发现成熟大脑中亚板细胞的作用，也没有系统地分析亚板特异性基因的疾病相关性。在这里，我们提出了基因表达的证据，小鼠亚板在整个发展过程中的独特作用，以及独特的分子标记，以扩大亚板标签的剧目。进行系统的比较不同的年龄（胚胎15和18天，出生后8天，成人），我们揭示了动态和恒定的功能标记亚板细胞在胚胎和出生后早期的发展和成人。这可以使用https://molnar.dpag.ox.ac.uk/subplate/上的亚板基因表达的在线数据库来可视化。我们还确定了胚胎之间的心室区，中间区，基板，基板，第5层，第2/3层之间的基因表达的相似性和不同的出生后的相似性。在发育过程中的某个时刻，以亚板特异性方式表达的基因显示出与自闭症谱系障碍和精神分裂症相关的统计学显著富集。我们的报告强调了研究发育中大脑的短暂特征对更好地理解神经发育障碍的重要性。
The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as in the development of inhibitory cortical circuits in sensory areas. So far no role has been identified for cells in the subplate in the mature brain and disease association of the subplate-specific genes has not been analyzed systematically. Here we present gene expression evidence for distinct roles of the mouse subplate across development as well as unique molecular markers to extend the repertoire of subplate labels. Performing systematic comparisons between different ages (embryonic days 15 and 18, postnatal day 8, and adult), we reveal the dynamic and constant features of the markers labeling subplate cells during embryonic and early postnatal development and in the adult. This can be visualized using the online database of subplate gene expression at https://molnar.dpag.ox.ac.uk/subplate/. We also identify embryonic similarities in gene expression between the ventricular zones, intermediate zone, and subplate, and distinct postnatal similarities between subplate, layer 5, and layers 2/3. The genes expressed in a subplate-specific manner at some point during development show a statistically significant enrichment for association with autism spectrum disorders and schizophrenia. Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders.