The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.
The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.
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DOI：
10.3389/fnins.2014.00346
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发表时间：
2014
影响因子：
4.3
通讯作者：
Bainton RJ
中科院分区：
文献类型：
--
作者：
DeSalvo MK;Hindle SJ;Rusan ZM;Orng S;Eddison M;Halliwill K;Bainton RJ
中枢神经系统(CNS)的功能依赖于暴露在CNS空间的代谢物、药物、细胞和病原体的严格调控。细胞血脑屏障(BBB)结构是高度特异的检查点，控制着所有小分子进出大脑间质空间，但调节BBB的确切机制尚不清楚。此外，血脑屏障长期以来一直是中枢神经系统疾病药物治疗的一个具有挑战性的障碍；因此，非常需要能够解析血脑屏障功能的模型系统。在这项研究中，我们试图通过荧光激活细胞分选(FACS)分离成年果蝇BBB表面神经胶质细胞并用微阵列分析它们的基因表达，从而确定成年果蝇BBB的转录组。通过将这些表面胶质细胞的转录组与所有大脑胶质细胞、脑神经元和整个大脑的转录组进行比较，我们提供了一份选择性地在果蝇血脑屏障中浓缩的转录物的目录。我们发现，苍蝇表面胶质细胞高表达多种三磷酸腺苷结合盒(ABC)和溶质载体(SLC)转运体、细胞黏附分子、代谢酶、信号分子和异源代谢途径的组成部分。利用基于基因序列的比对，我们比较了果蝇和小鼠的BBB转录本，发现了许多共同的化学保护和小分子控制途径，从而肯定了无脊椎动物模型与研究进化保守的BBB属性的相关性。果蝇BBB转录组对于脊椎动物和昆虫生物学家来说都是很有价值的资源，可以作为研究扩散屏障发育和维持、神经胶质生物学和组织屏障药物转运调节的蛋白质的资源。
Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with fluorescence activated cell sorting (FACS) and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ATP-binding cassette (ABC) and solute carrier (SLC) transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.
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