Hmga2 is required for neural crest cell specification in Xenopus laevis
Hmga2 is required for neural crest cell specification in Xenopus laevis
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DOI：
10.1016/j.ydbio.2016.01.014
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发表时间：
2016-03-01
影响因子：
2.7
通讯作者：
Vignali, Robert
中科院分区：
文献类型：
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作者：
Macri, Simone;Simula, Luca;Vignali, Robert
HMGA蛋白是通过保守的AT-钩基序结合DNA、修饰染色质结构并辅助基因表达的小核蛋白。两种HMGA（HMGA 1和HMGA 2），由不同的基因编码，存在于哺乳动物中，并在胚胎发生过程中高度表达或在肿瘤进展中重新激活。我们在这里解决了在体内的作用，非洲爪蟾hmga 2的神经嵴细胞（NCCs）。我们发现，hmga 2是需要正常的NCC规范和发展。hmga 2敲低导致前部NCC的主要骨骼衍生物的严重破坏。我们发现，在NCC遗传网络中，hmga 2作用于msx 1的下游，并且是msx 1，pax 3和snail 2活动所必需的，从而参与网络的不同层次。由于hmga 2在NCC特化中的早期作用，随后的上皮-间充质转化（EMT）和NCC向鳃囊的迁移也受到损害。与胚胎上的结果严格平行，在乳腺癌细胞模型中干扰Hmga 2用于EMT导致的分子效应与在NCC上观察到的分子效应基本一致。这些数据表明，Hmga 2在NCC和肿瘤细胞共享的关键分子事件中被招募。(C)2016 Elsevier Inc. All rights reserved.
HMGA proteins are small nuclear proteins that bind DNA by conserved AT-hook motifs, modify chromatin architecture and assist in gene expression. Two HMGAs (HMGA1 and HMGA2), encoded by distinct genes, exist in mammals and are highly expressed during embryogenesis or reactivated in tumour progression. We here addressed the in vivo role of Xenopus hmga2 in the neural crest cells (NCCs). We show that hmga2 is required for normal NCC specification and development. hmga2 knockdown leads to severe disruption of major skeletal derivatives of anterior NCCs. We show that, within the NCC genetic network, hmga2 acts downstream of msx1, and is required for msxl, pax3 and snail2 activities, thus participating at different levels of the network. Because of hmga2 early effects in NCC specification, the subsequent epithelial-mesenchymal transition (EMT) and migration of NCCs towards the branchial pouches are also compromised. Strictly paralleling results on embryos, interfering with Hmga2 in a breast cancer cell model for EMT leads to molecular effects largely consistent with those observed on NCCs. These data indicate that Hmga2 is recruited in key molecular events that are shared by both NCCs and tumour cells. (C) 2016 Elsevier Inc. All rights reserved.