Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.
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DOI:
10.1371/journal.pone.0063218
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Henion PD
Henion PD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ignatius MS;Unal Eroglu A;Malireddy S;Gallagher G;Nambiar RM;Henion PD

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基因表达的调节是通过遗传和表观遗传手段来完成的,并且是精确控制神经嵴发育所必需的。在hdac1b382突变体中,颅面软骨发育在两个不同的方面有缺陷。首先,较少的hoxb3a,dlx2和dlx3表达后鳃弓前体被指定和许多因此进行细胞凋亡。第二,与此相反,正常数量的祖细胞存在于前下颌骨和舌骨弓,但软骨细胞前体未能最终分化。在外周神经系统中,与野生型胚胎相比,hdac1b382突变体中的肠、DRG和交感神经元分化被破坏。具体而言,肠和DRG前体分别分化成前肠和躯干中的神经元,而肠和DRG神经元很少存在于后肠和尾部中。交感神经元前体在hdac1b382突变体中被指定,它们经历一般的神经元分化,但不能经历去甲肾上腺素能分化。使用HDAC抑制剂TSA,我们分离的酶活性和时间要求HDAC功能再现hdac1b382缺陷颅面和交感神经元的发展。我们的研究揭示了斑马鱼hdac1在神经嵴衍生颅面神经元和外周神经元发育中的不同功能和时间需求。
The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.
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