Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
Am J Pathol. 2018 Feb;188(2):336-342. doi: 10.1016/j.ajpath.2017.10.004. Epub 2017 Nov 9.
Treacher Collins syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects. Recently, the authors' group unfolded the pathogenesis of polr1c Type 3 TCS by using the zebrafish model. Facial development depends on the neural crest cells, in which polr1c plays a role in regulating their expression. In this study, the authors aimed to identify the functional time window of polr1c in TCS by the use of photo-morpholino to restore the polr1c expression at different time points. Results suggested that the restoration of polr1c at 8 hours after fertilization could rescue the TCS facial malformation phenotype by correcting the neural crest cell expression, reducing the cell death, and normalizing the p53 mRNA expression level in the rescued morphants. However, such recovery could not be reproduced if the polr1c is restored after 30 hours after fertilization.
特雷彻·柯林斯综合征（TCS）是一种罕见的先天性出生缺陷（每 50,000 例活产中就有 1 例），其特征为严重的颅面缺陷。最近，作者小组利用斑马鱼模型揭示了 polr1c 型 3 型 TCS 的发病机制。面部发育依赖于神经嵴细胞，其中 polr1c 在调节其表达中发挥作用。在这项研究中，作者旨在通过使用光-Morpholino 在不同时间点恢复 polr1c 的表达来确定 TCS 中 polr1c 的功能时间窗。结果表明，在受精后 8 小时恢复 polr1c 可以通过纠正神经嵴细胞的表达、减少细胞死亡以及使获救的形态发生体中的 p53 mRNA 表达水平正常化，来挽救 TCS 面部畸形表型。然而，如果在受精后 30 小时后恢复 polr1c，则无法重现这种恢复。
