GATA4 as a novel regulator involved in the development of the neural crest and craniofacial skeleton via Barx1.

GATA4 as a novel regulator involved in the development of the neural crest and craniofacial skeleton via Barx1.
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GATA4 作为一种新型调节因子,通过 Barx1 参与神经嵴和颅面骨骼的发育。

DOI:
10.1038/s41418-018-0083-x
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发表时间:
2018-11
影响因子:
12.4
通讯作者:
Wang L
Wang L
中科院分区:
生物学1区
文献类型:
--
作者:
Guo S;Zhang Y;Zhou T;Wang D;Weng Y;Chen Q;Ma J;Li YP;Wang L

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GATA结合蛋白4(GATA 4)在神经嵴细胞(NCC)中的作用尚不清楚。在这里,我们发现缺乏GATA 4的小鼠NCC在颅面骨、牙齿和心脏中表现出发育缺陷。这些缺陷可能是由于发育阶段细胞增殖减少而发生的。体外结果与小鼠模型一致。同源异型标签的相对和绝对定量分析表明,BARX1是NCC中GATA 4敲低后差异表达的蛋白质之一。双荧光素酶,电迁移率变化,染色质免疫沉淀试验的结果的基础上,Barx 1的表达直接调控GATA 4在NCC。在斑马鱼中,gata4敲低影响NCC衍生物的发育。然而,在斑马鱼的表型可以通过共注射gata4 morpholino寡聚体和barx 1 mRNA部分拯救。这项研究确定了NCC中GATA 4的新下游靶点,并发现了GATA 4在NCC发展中复杂调控功能的额外证据。
The role of GATA-binding protein 4 (GATA4) in neural crest cells (NCCs) is poorly defined. Here we showed that mouse NCCs lacking GATA4 exhibited developmental defects in craniofacial bone, teeth, and heart. The defects likely occurred due to decreased cell proliferation at the developmental stage. The in vitro results were consistent with the mouse model. The isobaric tags for relative and absolute quantitation assay revealed that BARX1 is one of the differentially expressed proteins after GATA4 knockdown in NCCs. On the basis of the results of dual-luciferase, electro-mobility shift, and chromatin immunoprecipitation assays, Barx1 expression is directly regulated by GATA4 in NCCs. In zebrafish, gata4 knockdown affects the development of NCCs derivatives. However, the phenotype in zebrafish could be partly rescued by co-injection of gata4 morpholino oligomers and barx1 mRNA. This study identified new downstream targets of GATA4 in NCCs and uncovered additional evidence of the complex regulatory functions of GATA4 in NCC development.
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