Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.
Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.
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DOI：
10.1002/dvdy.24563
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Trivedi CM
中科院分区：
文献类型：
--
作者：
Milstone ZJ;Lawson G;Trivedi CM
颅面畸形涉及咽弓发育和神经嵴功能缺陷。在1 p35的拷贝数变异，含有组蛋白脱乙酰酶1（Hdac 1），或6 q21 -22，含有Hdac 2，涉及颅面缺陷的患者，这表明在指导神经嵴发育的重要作用。然而，Hdac 1和Hdac 2在神经嵴细胞中的作用仍然未知。神经嵴及其衍生物在早期小鼠发育过程中表达Hdac 1和Hdac 2。小鼠神经嵴祖细胞内Hdac 1和Hdac 2的消融导致严重出血、萎缩的咽弓、有缺陷的头部形态发生和完全的胚胎致死。神经嵴中缺乏Hdac 1和Hdac 2的胚胎表现出神经管和第一咽弓的增殖减少和凋亡增加。从机制上讲，Hdac 1和Hdac 2的缺失上调细胞周期蛋白依赖性激酶抑制剂Cdkn 1a、Cdkn 1b、Cdkn 1c、Cdkn 2b、Cdkn 2c、我们的研究结果表明，Hdac 1和Hdac 2在神经嵴内具有冗余功能，调节咽弓的增殖和发育通过抑制细胞周期蛋白依赖性激酶抑制剂。
Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches via repression of cyclin-dependent kinase inhibitors.
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