Rescue of neural crest-derived phenotypes in a zebrafish CHARGE model by Sox10 downregulation
Rescue of neural crest-derived phenotypes in a zebrafish CHARGE model by Sox10 downregulation
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DOI：
10.1093/hmg/ddw198
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发表时间：
2016-08-15
影响因子：
3.5
通讯作者：
Sachidanandan, Chetana
中科院分区：
文献类型：
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作者：
Asad, Zainab;Pandey, Aditi;Sachidanandan, Chetana
CHD 7突变与先天性疾病CHARGE综合征的大多数病例有关。CHARGE是一种常染色体显性遗传综合征，已知会影响多种组织，包括眼、心脏、耳、颅面神经以及骨骼和生殖器官。使用基于morpholino-antisense-alcohol tide的斑马鱼CHARGE综合征模型，我们发现了神经嵴和嵴源性细胞类型的复杂异常谱。我们报告的第一次，髓鞘雪旺细胞，肠神经元和色素细胞的缺陷在一个充电模型。我们还观察到缺陷的规格的外周神经元和颅面骨骼如前所述。chd 7吗啡变体从早期阶段就损害了神经嵴细胞的迁移和sox 10表达的失调。在斑马鱼CHARGE模型中敲低Sox 10挽救了雪旺细胞和颅面软骨的缺陷。因此，我们的斑马鱼CHARGE模型揭示了Chd 7在神经嵴发育的多个点上的重要调控作用，迁移，命运选择和分化，我们认为，sox 10失调是一个重要的驱动程序的神经嵴衍生方面的Chd 7依赖性CHARGE综合征。
CHD7 mutations are implicated in a majority of cases of the congenital disorder, CHARGE syndrome. CHARGE, an autosomal dominant syndrome, is known to affect multiple tissues including eye, heart, ear, craniofacial nerves and skeleton and genital organs. Using amorpholino-antisense-oligonucleotide-based zebrafish model for CHARGE syndrome, we uncover a complex spectrum of abnormalities in the neural crest and the crest-derived cell types. We report for the first time, defects in myelinating Schwann cells, enteric neurons and pigment cells in a CHARGE model. We also observe defects in the specification of peripheral neurons and the craniofacial skeleton as previously reported. Chd7 morphants have impaired migration of neural crest cells and deregulation of sox10 expression from the early stages. Knocking down Sox10 in the zebrafish CHARGE model rescued the defects in Schwann cells and craniofacial cartilage. Our zebrafish CHARGE model thus reveals important regulatory roles for Chd7 at multiple points of neural crest development viz., migration, fate choice and differentiation and we suggest that sox10 deregulation is an important driver of the neural crest-derived aspects of Chd7 dependent CHARGE syndrome.