探索小鼠視覺皮質層中抑制性神經元的印記體

Abstract

基因體印記（genomic imprinting）是被歸類在表觀遺傳學（Epigenetics）裡的現象，主要是藉由甲基化的修飾，造成基因的表現會受父方或母方來源的等位基因 (allele)來影響。此現象主要發生在腦部，而且異常的印記基因（imprinted gene）與許多神經疾病有關。由此看來，基因體印記在腦部扮演著重要的角色，但並沒有一個全面性的研究，可以讓我們深入地了解其中的關連。因此在我們的研究中，中心目標是探討基因體印記在不同細胞型態、生長發育階段及環境條件的表現。此三種因素在之前的研究中，被發現可能會影響基因體印記的狀態。我們調控光線的有無來製造不同環境，發現許多印記基因在視網膜（retina）、視叉上核（Suprachiasmatic nucleus）、視覺皮層（visual cortex） （統稱為視覺系統）發生變化；其中我們發現一個負責調控微小核糖核酸（imprinted microRNA）的基因-Ago2可能是只有在腦部才會發生印記的情形。我們也觀察到可能是興奮性神經元、抑制性神經元、或星狀膠細胞特有的印記基因。另外，我們也對印記微小核糖核酸有興趣，因為之前的研究中發現有調控印記基因的功能。為了要研究此類微小核醣核酸的功能，我們建立了可以測量其表現量的系統。雖然此研究包含許多部份，但都圍繞在”基因體印記”這個主題。我們期許這樣廣泛性的研究可以了解印記基因在腦中的變化情形以及所扮演的角色。

Genomic imprinting refers to an epigenetic mark that distinguishes parental alleles and results in a monoallelic, parent-of-origin-specific expression pattern in mammals. Genomic imprinting occurs in the brain and dysfunctional imprinted genes cause various neurological and psychiatric disorders. Despite the important roles of genomic imprinting, the physiological roles of imprinted genes in the brain are still limited. To fully understand imprinted genes in brain, factors that may influence genomic imprinting status were considered in our study. Accordingly, our aim was to profile three dimensions of imprinting status in the brain: different cell types, developmental stages, and environmental condition. We used dark rearing system to manipulate environmental factors, and observed dynamic imprinted genes in visual system, including the retina, the suprachiasmatic nucleus (SCN), and the visual cortex (VC). Among of the imprinted genes, we are interested in Ago2 that was found to be a brain-specific imprinted gene. We also observed genes may be specifically imprinted in excitatory neurons, interneurons, or astrocytes. Additionally, we profiled imprinted miRNAs, which are able to regulate imprinted genes. To investigate miRNA function, a special quantification system was built. This study contains many parts, but they are all surrounding the subject “genomic imprinting”. We hope our study may enable us to learn more about the function and roles of genomic imprinting in the brain.