Nagase Takashi, Nagase Miki, Osumi Noriko, Fukuda Satoru, Nakamura Shun, Ohsaki Kanae, Harii Kiyonori, Asato Hirotaka, Yoshimura Kotaro
Department of Plastic and Reconstructive Surgery, University Hospital, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
J Craniofac Surg. 2005 Jan;16(1):80-8. doi: 10.1097/00001665-200501000-00016.
The pathogenesis of holoprosencephaly is multifactorial, and blockage of Sonic hedgehog signaling is one of the most important causative factors in animal models and human cases. In this study, the authors analyzed facial anomalies of mouse embryos, which were cultured in vitro and exposed to cyclopamine, an alkaloid blocker of Sonic hedgehog signaling. When cultured with cyclopamine for embryonic day 8.5 to 10.5, the whole body size was smaller than normal, and the distance and angle between the nasal placodes were remarkably reduced. Extension of the cranial surface vessels also was noted. No cyclopia was observed. Migration of the cranial neural crest cells seemed to be intact. Expressions of Patched-1 and Gli-1, downstream genes of Sonic hedgehog signaling, also were down-regulated in in situ hybridization and real-time reverse transcriptase-polymerase chain reaction analyses. The authors consider that these facial anomalies represent milder phenotypes of holoprosencephaly.
前脑无裂畸形的发病机制是多因素的，在动物模型和人类病例中，音猬因子信号通路的阻断是最重要的致病因素之一。在本研究中，作者分析了体外培养并暴露于环杷明（一种音猬因子信号通路的生物碱阻断剂）的小鼠胚胎的面部异常情况。在胚胎第8.5天至10.5天与环杷明一起培养时，全身尺寸小于正常，鼻基板之间的距离和角度显著减小。还注意到颅面血管的延伸。未观察到独眼畸形。颅神经嵴细胞的迁移似乎完好无损。在原位杂交和实时逆转录聚合酶链反应分析中，音猬因子信号通路的下游基因Patched-1和Gli-1的表达也下调。作者认为这些面部异常代表了前脑无裂畸形的较轻表型。
