Deciphering gene expression program of MAP3K1 in mouse eyelid morphogenesis.
Deciphering gene expression program of MAP3K1 in mouse eyelid morphogenesis.
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DOI：
10.1016/j.ydbio.2012.11.020
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发表时间：
2013-02-01
影响因子：
2.7
通讯作者：
Xia, Ying
中科院分区：
文献类型：
--
作者：
Jin, Chang;Chen, Jing;Meng, Qinghang;Carreira, Vinicius;Tam, Neville N. C.;Geh, Esmond;Karyala, Saikumar;Ho, Shuk-Mei;Zhou, Xiangtian;Medvedovic, Mario;Xia, Ying
胚胎眼睑闭合涉及上下眼睑的向前运动和最终融合，这是哺乳动物眼表发育的重要步骤。虽然其潜在的作用机制尚不完全清楚，但一种功能性丝裂原激活蛋白激酶激酶1 （MAP3K1）是眼睑闭合所必需的。本文研究MAP3K1在眼睑形态发生中的分子特征。在小鼠妊娠期E15.5，即闭合眼睑前的发育阶段，MAP3K1在眼睑前缘（LE）和内眼睑（IE）上皮中表达为主。我们使用激光捕获显微解剖（LCM）从野生型和map3k1缺陷胎儿中获得高富集的LE和IE细胞，并分析了全基因组表达谱。基因表达数据鉴定了MAP3K1的三个不同的发育特征。首先，MAP3K1仅在LE而非IE上皮中调节Wnt和Sonic hedgehog信号、肌动蛋白重组和增殖，说明了MAP3K1在胚胎发生中的时空特异性。其次，MAP3K1增强了AP-2α的表达以及SRF和AP-1的活性，但其靶基因富集了AP-2α和SRF的结合基序，而不是AP-1，这表明存在新的MAP3K1-AP-2α/SRF模块参与基因调控。第三，MAP3K1对LE和IE上皮中谱系特异性基因的表达有不同的影响，揭示了MAP3K1在分化和谱系规范中的潜在作用。利用LCM和表达阵列，我们的研究发现了MAP3K1在胚胎眼睑闭合中的新的分子特征。
Embryonic eyelid closure involves forward movement and ultimate fusion of the upper and lower eyelids, an essential step of mammalian ocular surface development. Although its underlying mechanism of action is not fully understood, a functional mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is required for eyelid closure. Here we investigate the molecular signatures of MAP3K1 in eyelid morphogenesis. At mouse gestational day E15.5, the developmental stage immediately prior to eyelid closure, MAP3K1 expression is predominant in the eyelid leading edge (LE) and the inner eyelid (IE) epithelium. We used Laser Capture Microdissection (LCM) to obtain highly enriched LE and IE cells from wild type and MAP3K1-deficient fetuses and analyzed genome-wide expression profiles. The gene expression data led to the identification of three distinct developmental features of MAP3K1. First, MAP3K1 modulated Wnt and Sonic hedgehog signals, actin reorganization, and proliferation only in LE but not in IE epithelium, illustrating the temporal-spatial specificity of MAP3K1 in embryogenesis. Second, MAP3K1 potentiated AP-2α expression and SRF and AP-1 activity, but its target genes were enriched for binding motifs of AP-2α and SRF, and not AP-1, suggesting the existence of novel MAP3K1-AP-2α/SRF modules in gene regulation. Third, MAP3K1 displayed variable effects on expression of lineage specific genes in the LE and IE epithelium, revealing potential roles of MAP3K1 in differentiation and lineage specification. Using LCM and expression array, our studies have uncovered novel molecular signatures of MAP3K1 in embryonic eyelid closure.
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影响因子：
14.9
作者：
Blake JA;Bult CJ;Eppig JT;Kadin JA;Richardson JE;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
影响因子：
11.4
作者：
Grotewold, L;Rüther, U
通讯作者：
Rüther, U
在没有刺猬信号的情况下，头发发育异常和明显的卵泡转化向乳腺。
影响因子：
11.8
作者：
Gritli-Linde, Amel;Hallberg, Kristina;Harfe, Brian D.;Reyahi, Azadeh;Kannius-Janson, Marie;Nilsson, Jeanette;Cobourne, Martyn T.;Sharpe, Paul T.;McMahon, Andrew P.;Linde, Anders
通讯作者：
Linde, Anders
DOI：
10.1073/pnas.1102297108
发表时间：
2011-10-18
影响因子：
11.1
作者：
Geh, Esmond;Meng, Qinghang;Xia, Ying
通讯作者：
Xia, Ying
影响因子：
2.5
作者：
DAVIS, RJ
通讯作者：
DAVIS, RJ