Expression Analyses of Mediator Complex Subunit 13-Like: A Responsible Gene for Neurodevelopmental Disorders during Mouse Brain Development
Expression Analyses of Mediator Complex Subunit 13-Like: A Responsible Gene for Neurodevelopmental Disorders during Mouse Brain Development
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DOI：
10.1159/000515188
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发表时间：
2021-04-01
影响因子：
2.9
通讯作者：
Nagata, Koh-ichi
中科院分区：
文献类型：
--
作者：
Hamada, Nanako;Iwamoto, Ikuko;Nagata, Koh-ichi
MED 13 L（mediator complex subunit 13-like）是介体复合物的一个组成部分，其功能是基因转录的调节因子。由于MED 13 L基因异常导致神经发育障碍，因此推测MED 13 L在大脑发育中起重要作用。在本研究中，我们制备了针对MED 13 L的特异性抗体，anti-MED 13 L，并分析了其在小鼠组织中的表达谱，重点是中枢神经系统。在Western blotting中，MED 13 L在成年小鼠中表现出组织依赖性的表达谱，并且在脑中以发育阶段依赖性的方式表达。在免疫荧光分析中，MED 13 L在原代培养的海马神经元中至少部分地与突触前和突触后标记物突触素和PSD 95共定位。免疫组化结果显示，MED 13 L在胚胎14 d时在大脑皮质的室带表面有较高的表达，在皮质板的神经元胞质和胞核中也有表达。然后，MED 13 L在出生后30天（P）在整个大脑皮质中显示弥漫性胞质分布。此外，MED 13 L似乎是本地化的细胞类型和发育阶段的具体方式在海马和小脑。这些结果表明，MED 13 L参与中枢神经系统的发育和突触功能。
MED13L (mediator complex subunit 13-like) is a component of the mediator complex, which functions as a regulator for gene transcription. Since gene abnormalities in MED13L are responsible for neurodevelopmental disorders, MED13L is presumed to play an essential role in brain development. In this study, we prepared a specific antibody against MED13L, anti-MED13L, and analyzed its expression profile in mouse tissues with focusing on the central nervous system. In Western blotting, MED13L exhibited a tissue-dependent expression profile in the adult mouse and was expressed in a developmental stage-dependent manner in brain. In immunofluorescence analyses, MED13L was at least partially colocalized with pre- and post-synaptic markers, synaptophysin, and PSD95, in primary cultured hippocampal neurons. Immunohistochemical analyses revealed that MED13L was relatively highly expressed in ventricular zone surface of cerebral cortex, and was also located both in the cytoplasm and nucleus of neurons in the cortical plate at embryonic day 14. Then, MED13L showed diffuse cytoplasmic distribution throughout the cerebral cortex at the postnatal day (P) 30. In addition, MED13L appeared to be localized in cell type- and developmental stage-specific manners in the hippocampus and cerebellum. These results suggest that MED13L is involved in the development of the central nervous system and synaptic function.