DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes.
DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes.
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DOI：
10.1371/journal.pone.0088506
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ito A
中科院分区：
文献类型：
--
作者：
Hattori T;Shimizu S;Koyama Y;Emoto H;Matsumoto Y;Kumamoto N;Yamada K;Takamura H;Matsuzaki S;Katayama T;Tohyama M;Ito A
精神分裂症1号紊乱基因（DISC1）是一个被易位破坏的基因，t(1;11) (q42.1;q14.3)，在一个苏格兰家庭中与主要精神疾病分离，包括精神分裂症、复发性重度抑郁症和双相情感障碍。本研究报道，哺乳动物少突胶质细胞内源性表达的DISC1负向调节少突胶质细胞前体细胞向少突胶质细胞的分化。小鼠胼胝体少突胶质细胞P14和P70表达DISC1。DISC1 mRNA在原代培养的大鼠皮质少突胶质前体细胞中表达，在PDGF剥夺诱导少突胶质前体细胞分化时表达减少。免疫细胞化学分析显示，过表达的DISC1定位于少突胶质细胞前体细胞和少突胶质细胞的细胞体和突起中。我们发现，髓磷脂相关标志物CNPase和MBP的表达，以及成熟少突胶质细胞形态的细胞数量，在全长DISC1过表达后减少。相反，通过RNA干扰敲低内源性DISC1后，CNPase的表达和成熟形态的少突胶质细胞数量均增加。截断形式DISC1的过表达也导致髓磷脂相关蛋白的表达增加和成熟少突胶质细胞的数量增加，可能通过显性负性机制起作用。我们还发现Sox10和Nkx2.2参与少突胶质细胞分化的DISC1调控途径，这两个众所周知的转录因子都参与髓磷脂基因的调控。
Disrupted-in-schizophrenia 1 (DISC1) is a gene disrupted by a translocation, t(1;11) (q42.1;q14.3), that segregates with major psychiatric disorders, including schizophrenia, recurrent major depression and bipolar affective disorder, in a Scottish family. Here we report that mammalian DISC1 endogenously expressed in oligodendroglial lineage cells negatively regulates differentiation of oligodendrocyte precursor cells into oligodendrocytes. DISC1 expression was detected in oligodendrocytes of the mouse corpus callosum at P14 and P70. DISC1 mRNA was expressed in primary cultured rat cortical oligodendrocyte precursor cells and decreased when oligodendrocyte precursor cells were induced to differentiate by PDGF deprivation. Immunocytochemical analysis showed that overexpressed DISC1 was localized in the cell bodies and processes of oligodendrocyte precursor cells and oligodendrocytes. We show that expression of the myelin related markers, CNPase and MBP, as well as the number of cells with a matured oligodendrocyte morphology, were decreased following full length DISC1 overexpression. Conversely, both expression of CNPase and the number of oligodendrocytes with a mature morphology were increased following knockdown of endogenous DISC1 by RNA interference. Overexpression of a truncated form of DISC1 also resulted in an increase in expression of myelin related proteins and the number of mature oligodendrocytes, potentially acting via a dominant negative mechanism. We also identified involvement of Sox10 and Nkx2.2 in the DISC1 regulatory pathway of oligodendrocyte differentiation, both well-known transcription factors involved in the regulation of myelin genes.
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影响因子：
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通讯作者：
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