Co-expression of C/EBPγ and ATF5 in mouse vomeronasal sensory neurons during early postnatal development
Co-expression of C/EBPγ and ATF5 in mouse vomeronasal sensory neurons during early postnatal development
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出生后早期发育过程中小鼠犁鼻感觉神经元中 C/EBPγ 和 ATF5 的共表达
DOI：
10.1007/s00441-019-03070-2
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发表时间：
2019
影响因子：
3.6
通讯作者：
Yuji Takahashi
中科院分区：
文献类型：
--
作者：
Haruo Nakano;Yoshitaka Iida;Takahiro Murase;Natsuki Oyama;Mariko Umemura;Shigeru Takahashi;Yuji Takahashi
感觉神经元的分化与特定转录因子诱导的基因表达变化有关。小鼠犁鼻器官（VNO）中的犁鼻感觉神经元（VSNs）由表达犁鼻1受体(V1r)/Gαi2或表达犁鼻2受体(V2r)/Gαo的两个主要神经元亚群组成，它们与一个共同的神经祖细胞不同。我们之前证明，在ATF5转录因子缺乏的小鼠中，VSNs的分化和存活受到抑制（Nakano等）。中国生物医学工程学报（英文版），2016)。这些缺陷在V2r/ g αo型中比在V1r/ g αi2型中更为突出；然而，ATF5诱导V2r/ g - αo型VSNs分化的分子机制尚不清楚。为了确定参与ATF5调控VSN分化的辅助因子，我们研究了CCAAT/增强子结合蛋白γ (C/EBPγ, Cebpg)的表达和功能，该蛋白是小鼠VNO中表达的主要C/EBP家族成员，与ATF5二聚体。结果显示，C/EBPγ mrna和蛋白在新生儿VNO的有丝分裂后vsn中广泛表达，并在出生后第2周表达减少。在新生儿VNO中，约70%的vsn细胞核中表达C/EBPγ蛋白，20%的vsn共表达C/EBPγ和ATF5蛋白。我们研究了C/EBPγ和ATF5对V2r转录的反式作用，发现C/EBPγ和ATF5共同表达，而不是C/EBPγ或ATF5单独表达，通过C/EBP:ATF反应元件（CARE）在Neuro2a细胞中增加Vmn2r66启动子报告子活性。这些结果表明，C/EBPγ在atf5调控的VSN分化中起着重要作用。
The differentiation of sensory neurons involves gene expression changes induced by specific transcription factors. Vomeronasal sensory neurons (VSNs) in the mouse vomeronasal organ (VNO) consist of two major subpopulations of neurons expressing vomeronasal 1 receptor (V1r)/Gαi2 or vomeronasal 2 receptor (V2r)/Gαo, which differentiate from a common neural progenitor. We previously demonstrated that the differentiation and survival of VSNs were inhibited in ATF5 transcription factor-deficient mice (Nakano et al. Cell Tissue Res 363:621–633, 2016). These defects were more prominent in V2r/Gαo-type than in V1r/Gαi2-type VSNs; however, the molecular mechanisms responsible for the differentiation of V2r/Gαo-type VSNs by ATF5 remain unclear. To identify a cofactor involved in ATF5-regulated VSN differentiation, we investigated the expression and function of CCAAT/enhancer-binding protein gamma (C/EBPγ, Cebpg), which is a major C/EBP family member expressed in the mouse VNO and dimerizes with ATF5. The results obtained showed that C/EBPγ mRNAs and proteins were broadly expressed in the postmitotic VSNs of the neonatal VNO, and their expression decreased by the second postnatal week. The C/EBPγ protein was expressed in the nuclei of approximately 70% of VSNs in the neonatal VNO, and 20% of the total VSNs co-expressed C/EBPγ and ATF5 proteins. We examined the trans-acting effects of C/EBPγ and ATF5 on V2r transcription and found that the co-expression of C/EBPγ and ATF5, but not C/EBPγ or ATF5 alone, increased Vmn2r66 promoter reporter activity via the C/EBP:ATF response element (CARE) in Neuro2a cells. These results suggest the role of C/EBPγ on ATF5-regulated VSN differentiation in early postnatal development.