The epigenetic modifier DNMT3A is necessary for proper otic placode formation.
The epigenetic modifier DNMT3A is necessary for proper otic placode formation.
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DOI：
10.1016/j.ydbio.2016.01.034
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发表时间：
2016-03-15
影响因子：
2.7
通讯作者：
Bronner ME
中科院分区：
文献类型：
--
作者：
Roellig D;Bronner ME
头盖骨是外胚层的增厚，形成脊椎动物头部的感觉器官和外周神经节。在原肠胚期和神经胚期，胎盘前体与未来的神经和神经脊细胞混合在神经板的边界。在这里，我们展示了表观遗传修饰物，DNA甲基转移酶(DNMT)3A，表达在神经板边缘区域，影响耳道胎盘的发育，这将有助于耳朵。DNMT3A在原肠胚至神经胚期的推定区域表达，随后在耳胎盘本身表达。虽然神经板边缘和非神经外胚层标记Erni、Dlx5、Msx1和SIx1没有改变，但DNMT3A功能的丧失导致关键耳科胎盘指定子基因Pax2和Gbx2以及后来的耳科标记Sox10和Soho1的表达早期减少。在HH7首次观察到Gbx2的减少，远远早于其他耳聋标志物的丢失。后来，这转化为耳泡的大小显著减小。基于这些结果，我们认为DNMT3A对于激活Gbx2表达是重要的，而Gbx2是内耳正常发育所必需的。
Cranial placodes are thickenings in the ectoderm that give rise to sensory organs and peripheral ganglia of the vertebrate head. At gastrula and neurula stages, placodal precursors are intermingled in the neural plate border with future neural and neural crest cells. Here, we show that the epigenetic modifier, DNA methyl transferase (DNMT) 3A, expressed in the neural plate border region, influences development of the otic placode which will contribute to the ear. DNMT3A is expressed in the presumptive otic region at gastrula through neurula stages and later in the otic placode itself. Whereas neural plate border and non-neural ectoderm markers Erni, Dlx5, Msx1 and Six1 are unaltered, DNMT3A loss of function leads to early reduction in the expression of the key otic placode specifier genes Pax2 and Gbx2 and later otic markers Sox10 and Soho1. Reduction of Gbx2 was first observed at HH7, well before loss of other otic markers. Later, this translates to significant reduction in the size of the otic vesicle. Based on these results, we propose that DNMT3A is important for enabling the activation of Gbx2 expression, necessary for normal development of the inner ear.