Xenopus ADAM19 is involved in neural, neural crest and muscle development.

Xenopus ADAM19 is involved in neural, neural crest and muscle development.
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DOI:
10.1016/j.mod.2008.10.010
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发表时间:
2009-03
影响因子:
2.6
通讯作者:
Alfandari, Dominique
Alfandari, Dominique
中科院分区:
生物学4区
文献类型:
--
作者:
Neuner, Russell;Cousin, Helene;McCusker, Catherine;Coyne, Michael;Alfandari, Dominique

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ADAM19是ADAM金属蛋白酶meltrin亚家族的成员。在非洲爪蟾中,ADAM19以母体转录本的形式存在。合子表达开始于原肠胚形成期间,并在胚孔背面唇部明显。ADAM19在神经管、脊索和体体等背侧结构中通过神经发育和尾芽形成表达丰富。利用morpholino敲除,我们发现在原肠胚期胚胎中ADAM19蛋白的减少导致脊索中Brachyury表达减少,同时背侧标记物Goosecoid和Chordin表达增加。这些基因表达的变化伴随着磷酸化AKT (EGF信号通路的下游靶点)的减少,并且在囊胚以与对照胚胎相同的速度关闭时发生。在神经发育和尾芽形成过程中,ADAM19的敲除诱导神经标记物n -微管蛋白和NRP1的减少,但不诱导Sox2的减少。在体裂中胚层,MLC的表达也减少,而MyoD的表达没有减少。ADAM19的敲除也减少了细胞迁移前的神经嵴标记物。用EGF受体抑制剂处理的胚胎神经嵴诱导也减少,这表明该途径是神经嵴细胞诱导所必需的。通过靶向敲除ADAM19,我们发现神经和神经嵴标记物的减少是细胞自主的,如果颅神经嵴受到干扰,则迁移是细胞自主的。我们进一步发现,ADAM19蛋白的减少会影响体的组织,降低12-101的表达,并扰乱体间边界的纤维连接蛋白定位。
ADAM19 is a member of the meltrin subfamily of ADAM metalloproteases. In Xenopus, ADAM19 is present as a maternal transcript. Zygotic expression starts during gastrulation and is apparent in the dorsal blastopore lip. ADAM19 expression through neurulation and tailbud formation becomes enriched in dorsal structures such as the neural tube, the notochord and the somites. Using morpholino knock-down, we show that a reduction of ADAM19 protein in gastrula stage embryos results in a decrease of Brachyury expression in the notochord concomitant with an increase in the dorsal markers, Goosecoid and Chordin. These changes in gene expression are accompanied by a decrease in phosphorylated AKT, a downstream target of the EGF signaling pathway, and occur while the blastopore closes at the same rate as the control embryos. During neurulation and tailbud formation, ADAM19 knock-down induces a reduction of the neural markers N-tubulin and NRP1 but not Sox2. In the somitic mesoderm, the expression of MLC is also decreased while MyoD is not. ADAM19 knockdown also reduces neural crest markers prior to cell migration. Neural crest induction is also decreased in embryos treated with an EGF receptor inhibitor suggesting that this pathway is necessary for neural crest cell induction. Using targeted knockdown of ADAM19 we show that the reduction of neural and neural crest markers is cell autonomous and that the migration if the cranial neural crest is perturbed. We further show that ADAM19 protein reduction affects somite organization, reduces 12–101 expression and perturbs fibronectin localization at the intersomitic boundary.
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期刊: The Journal of cell biology
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发表时间: 1998-05-01
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DOI: 10.1083/jcb.200602062
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