In recent years, Disrupted-In-Schizophrenia 1 (DISC1) has emerged as one of the most promising candidate genes whose disruption confers an increased risk for schizophrenia. Cell biology studies have implicated DISC1 in key neurodevelopmental processes including neurite outgrowth and neuronal migration. In situ hybridization analysis has revealed that Disc1 is expressed in the hypothalamus, olfactory bulbs, the developing cerebral cortex and the hippocampus. The hippocampus is of particular interest because abnormalities in hippocampal volume and function have been consistently reported in schizophrenics. Moreover, DISC1 mutations have been associated with abnormal activation of the hippocampus in humans. Given the involvement of the hippocampus in the pathophysiology of schizophrenia, there is an intriguing possibility that disruption of DISC1 may increase schizophrenia susceptibility by altering the normal development and function of the hippocampus. In order to contribute to our understanding of DISC1's role in the hippocampus, we have performed a detailed analysis of the Disc1 expression pattern in the mouse hippocampus throughout development. We report that Disc1 is expressed throughout the hippocampus during embryonic development, with expression becoming increasingly specialized in Ammon's horn and dentate gyrus granule cells within the first postnatal week. This expression pattern remains consistent into adulthood, with a noted decrease in Disc1 expression in the adult CA1. Disc1 is also expressed in proliferating cells in the adult subgranular zone, as well as in a subset of GABAergic interneurons. Our results are the first report of a detailed immunohistochemical analysis of the ontogeny of Disc1 expression within the hippocampus.

中文翻译：

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Disc1在发育中和成年海马中的表达的免疫组织化学分析。

近年来，精神分裂症中断基因1（DISC1）已成为最有希望的候选基因之一，其破坏会增加精神分裂症的风险。细胞生物学研究已将DISC1牵涉到主要的神经发育过程，包括神经突生长和神经元迁移。原位杂交分析表明，Disc1在下丘脑，嗅球，发育中的大脑皮层和海马中表达。海马特别令人感兴趣，因为在精神分裂症患者中一直报告有海马体积和功能异常。而且，DISC1突变与人类海马的异常激活有关。考虑到海马参与了精神分裂症的病理生理，DISC1的破坏可能通过改变海马的正常发育和功能而增加精神分裂症的易感性，这是一个令人着迷的可能性。为了有助于我们了解DISC1在海马中的作用，我们在整个发育过程中对小鼠海马中Disc1表达模式进行了详细分析。我们报告说，Disc1在胚胎发育过程中在整个海马中表达，在出生后的第一周内，表达变得越来越专门于Ammon的角和齿状回颗粒细胞。这种表达模式在成年后一直保持一致，在成年CA1中Disc1表达明显下降。Disc1也在成年亚颗粒区的增殖细胞以及GABA能中间神经元的子集中表达。