BIOSYNTHETIC ACTIVITY OF THE CHOROID PLEXUS

脉络丛（CP）形成血液的主要界面， 脑脊液（CSF）屏障，负责分泌 一大部分脑脊液 最近的研究表明， CP的生物合成活性，这表明CP也起着重要的作用。 在确定CSF的大分子含量中起重要作用。 我们（和 其他人）已经证明了特异性和丰富的合成 甲状腺素运载蛋白（TTR，前白蛋白），一种甲状腺素的转运蛋白， 视黄醇，在CP上皮内。 我们还描述了合成 胰岛素样生长因子II（IGF-II），一种携带胎儿有丝分裂原的 CP上皮与胰岛素原结构相似， 成年大鼠大脑的软脑膜。 的mRNA的存在 对于转铁蛋白、铜蓝蛋白和β-淀粉样蛋白， 报告，我们已经表明，通过免疫组织化学， CP内的几种其他专门的酶和血浆蛋白。 综上所述，这些数据表明，CP是一个重要的 大脑外部环境组成的决定因素。 我建议进行三大调查， 前期工作：1）成熟CP中的基因表达。 我们将扩大 研究CP的生物合成库，从而产生一个 CP表达基因探针组。 在某些情况下（如TTR和IGF- II），我们将开始研究其生理意义， CNS内合成。 2)CP的发展研究。 小组 CP DNA探针将用于研究基因表达模式， 发展CP。 这项建议的一个主要重点是试图发展 用于研究CP的形态发生的体外系统。 的 我们现有探针的特异性表明了一种新的方法， 问题：通过共同培养心室室管膜和软脑膜， 试图模拟CP的分化，如通过起始 TTR的从头合成。 3)CP的肿瘤。 CP基因组 将用于研究人类CP肿瘤中的基因表达 和动物 人CP乳头状瘤和SV 40/转基因小鼠模型 多灶性CP乳头状瘤将研究向上或向下的模式， 调控基因 在相关的情况下（如IGF-II），其他脑肿瘤将 也被研究。 在所有上述，在我们以前的工作，经典 分子遗传学技术将得到补充， 形态学技术，包括免疫组织化学和原位 杂交方法

The choroid plexus (CP) forms a major interface of the blood- cerebrospinal fluid (CSF) barrier and is responsible for the secretion of a large fraction of the CSF. Recent work has demonstrated important biosynthetic activities of the CP, suggesting that the CP also plays a vital role in determining the macromolecular content of the CSF. We (and others) have demonstrated the specific and abundant synthesis of transthyretin (TTR, prealbumin), a transport protein for thyroxine and retinol, within the CP epithelium. We have also described the synthesis of insulin-like growth factor II (IGF-II), a fetal mitogen bearing structural similarity to proinsulin, by the CP epithelium and leptomeningeal membranes of the adult rat brain. The presence of mRNA for transferrin, ceruloplasmin and the beta-preamylod protein have been reported, and we have shown, by immunohistochemistry, the presence of several other specialized enzymes and plasma proteins within the CP. Taken together, these data suggest that the CP is an important determinant of the composition of the external milieu of the brain. I propose to pursue three major lines of investigation deriving from our previous work: 1) Gene expression in the mature CP. We will expand the study of the biosynthetic repertoire of the CP, thereby generating a panel of CP-expressed gene probes. In selected cases (eg. TTR and IGF- II), we will begin to investigate the physiological significance of their intra-CNS synthesis. 2) Developmental studies of the CP. The panel of CP DNA probes will be used to study patterns of gene expression in the developing CP. A major focus of this proposal is an attempt to develop an in-vitro system for studying the morphogenesis of the CP. The specificity of our available probes suggests a novel approach to this question: by co-culturing ventricular ependyma and leptomeninges and attempting to simulate differentiation of the CP, as assayed by the onset of de novo TTR synthesis. 3) Neoplasia of the CP. The CP gene panel will be employed to study gene expression in tumors of the CP in humans and animals. Human CP papillomas and the SV40/transgenic mouse model of multifocal CP papillomas will be studied for patterns of up- or down- regulated genes. Where relevant (eg. IGF-II), other brain tumors will also be studied. In all of the above, as in our previous work, classic molecular gentic techniques will be complemented by a strong emphasis on morphological techniques, including immunohistochemistry and in situ hybridization.