EphA/ephrin-A signaling is critically involved in region-specific apoptosis during early brain development
EphA/ephrin-A signaling is critically involved in region-specific apoptosis during early brain development
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DOI：
10.1038/cdd.2012.121
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发表时间：
2013-01-01
影响因子：
12.4
通讯作者：
Park, S.
中科院分区：
文献类型：
--
作者：
Park, E.;Kim, Y.;Park, S.
EphAs和肝配蛋白-As与发育中的脑的形态发生有关。我们发现EphA 7和ephrin-A5在间脑和中脑前部的背中线（DM）共表达。有趣的是，在ephrin-A5/ephrin-A2双缺陷胚胎中，通常在该区域发现的神经上皮细胞的程序性细胞死亡（PCD）减少。相反，在体内表达的ephrin-A5-Fc或全长ephrin-A5强烈诱导神经上皮细胞凋亡，并伴随着严重的脑畸形在胚胎发育过程中。ephrinA 5-Fc的表达与EphA 7表达细胞的凋亡相关，而ephrin-A5的无效突变导致匡威的表型。重要的是，caspase-3或内源性ephrin-A5的无效突变减弱了异位过表达ephrin-A5诱导的PCD。总之，我们的研究结果表明，大脑区域特异性PCD可能发生在一个区域，其中EphAs集群与相邻的肝配蛋白-As通过细胞-细胞接触。Cell Death and Differentiation（2013）20，169-180; doi：10.1038/cdd.2012.121; 2012年9月14日在线发表
EphAs and ephrin-As have been implicated in the morphogenesis of the developing brain. We found that EphA7 and ephrin-A5 are coexpressed in the dorsal midline (DM) of the diencephalon and anterior mesencephalon. Interestingly, programmed cell death (PCD) of the neural epithelial cells normally found in this region was reduced in ephrin-A5/ephrin-A2 dual-deficient embryos. In contrast, in vivo expression of ephrin-A5-Fc or full-length ephrin-A5 strongly induced apoptosis in neural epithelial cells and was accompanied by severe brain malformation during embryonic development. Expression of ephrinA5-Fc correlated with apoptosis of EphA7-expressing cells, whereas null mutation of ephrin-A5 resulted in the converse phenotype. Importantly, null mutation of caspase-3 or endogenous ephrin-A5 attenuated the PCD induced by ectopically overexpressed ephrin-A5. Together, our results suggest that brain region-specific PCD may occur in a region where EphAs cluster with neighboring ephrin-As through cell-cell contact. Cell Death and Differentiation (2013) 20, 169-180; doi:10.1038/cdd.2012.121; published online 14 September 2012