The chromatin remodeler chd5 is necessary for proper head development during embryogenesis of Danio rerio
The chromatin remodeler chd5 is necessary for proper head development during embryogenesis of Danio rerio
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DOI：
10.1016/j.bbagrm.2015.06.006
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发表时间：
2015-08-01
影响因子：
4.7
通讯作者：
Ogas, Joe
中科院分区：
文献类型：
--
作者：
Bishop, Brett;Ho, Kwok Ki;Ogas, Joe
染色质重塑蛋白CHD5在哺乳动物的肿瘤抑制和神经发生中起关键作用。CHD5有助于神经发生过程中的基因表达，但关于这类重塑因子如何有助于分化和发育，仍有很多东西需要了解。CHD5重塑是脊椎动物特异性的，提出了CHD5在该门中起一个或多个保守作用的前景。chd5在成鱼中的表达密切反映了CHD5在成年哺乳动物中的表达。在胚胎发生过程中Chd 5的敲低表明了基于颅面发育中所产生的缺陷的CHD 5重塑的新作用，包括头部和眼睛尺寸减小以及头部软骨形成减少。此外，Chd 5的敲除导致发育中的脑和眼中神经标记物的表达改变，以及多巴胺能无长突细胞分化的严重缺陷。重组斑马鱼Chd5蛋白在体外表现出核小体重塑活性，这表明正是这种活性的丧失导致了所观察到的表型。我们的研究表明，斑马鱼是一个合适的模型，在脊椎动物中的CHD5重塑的功能表征，并强调了这种模型的潜力，产生新的见解，这类重要的重塑的作用。(C)2015爱思唯尔B.V.保留所有权利。
The chromatin remodeler CHD5 plays a critical role in tumor suppression and neurogenesis in mammals. CHD5 contributes to gene expression during neurogenesis, but there is still much to learn regarding how this class of remodelers contributes to differentiation and development. CHD5 remodelers are vertebrate-specific, raising the prospect that CHD5 plays one or more conserved roles in this phylum. Expression of chd5 in adult fish closely mirrors expression of CHD5 in adult mammals. Knockdown of Chd5 during embryogenesis suggests new roles for CHD5 remodelers based on resulting defects in craniofacial development including reduced head and eye size as well as reduced cartilage formation in the head. In addition, knockdown of Chd5 results in altered expression of neural markers in the developing brain and eye as well as a profound defect in differentiation of dopaminergic amacrine cells. Recombinant zebrafish Chd5 protein exhibits nucleosome remodeling activity in vitro, suggesting that it is the loss of this activity that contributes to the observed phenotypes. Our studies indicate that zebrafish is an appropriate model for functional characterization of CHD5 remodelers in vertebrates and highlight the potential of this model for generating novel insights into the role of this vital class of remodelers. (C) 2015 Elsevier B.V. All rights reserved.