Yasuda Y, Itoh K, Mizuno N, Konishi H, Tanimura T
Department of Anatomy (1st Division), Kiniki University School of Medicine, Osaka, Japan.
Anal Cell Pathol. 1989 Dec;2(1):23-40.
Alterations in migrating neural crest cells induced by all-trans retinoic acid (RA) were studied morphologically and immunohistochemically in the cranial portion of 8-day-old mouse embryos which were derived from dams given 60, 40 or 0 mg kg of RA and killed 2 to 8 h later. Additionally, the embryos exposed to 4 mg/kg of actinomycin D (AD) on day 8 of gestation for 5 h were examined similarly. Light microscopy revealed that RA was cytotoxic and caused the appearance of pleomorphic nuclei, extra-large nucleoli and cytoplasmic budding which replaced lamellipodia and spike-like projections. Electron microscopy revealed pleomorphic nuclei containing nucleoli with major granular portions frequently surrounded with heterochromatin, monosomes, and phagosomes. A monosomal distribution pattern was different from that seen in the neural crest cells exposed to AD. The latter showed incomplete polyribosomal dispersion with fewer nucleolar components. Fewer neural crest cells with choline acetyltransferase-like immunoreactivity were detected in RA- and AD-exposed embryos than in the controls. These findings suggest that excess RA inhibits acetylcholine synthesis of the migrating neural crest cells, in a manner different from AD, and that it enhances phagocytosis. These phenomena modify the characteristics of neural crest cells resulting in craniofacial malformations.
在给予60、40或0毫克/千克视黄酸（RA）的母鼠所产的8日龄小鼠胚胎的颅部，对全反式视黄酸（RA）诱导的迁移神经嵴细胞变化进行了形态学和免疫组织化学研究，并在2至8小时后处死。此外，对妊娠第8天暴露于4毫克/千克放线菌素D（AD）5小时的胚胎进行了类似检查。光学显微镜显示，RA具有细胞毒性，导致出现多形核、超大核仁和细胞质芽，取代了片状伪足和刺状突起。电子显微镜显示多形核含有核仁，主要颗粒部分经常被异染色质、单核糖体和吞噬体包围。单核糖体分布模式与暴露于AD的神经嵴细胞不同。后者显示多核糖体分散不完全，核仁成分较少。与对照组相比，在暴露于RA和AD的胚胎中，检测到具有胆碱乙酰转移酶样免疫反应性的神经嵴细胞较少。这些发现表明，过量的RA以不同于AD的方式抑制迁移神经嵴细胞的乙酰胆碱合成，并增强吞噬作用。这些现象改变了神经嵴细胞的特性，导致颅面畸形。
