Papalopulu N, Clarke J D, Bradley L, Wilkinson D, Krumlauf R, Holder N
MRC National Institute for Medical Research, Mill Hill, London, UK.
Development. 1991 Dec;113(4):1145-58. doi: 10.1242/dev.113.4.1145.
Retinoic acid is a very potent teratogen and has also been implicated as an endogenous developmental signalling molecule in vertebrate embryos. One of the regions of the embryo reliably affected by exogenously applied RA is the hindbrain. In this paper, we describe in detail the hindbrain of Xenopus laevis embryos briefly treated with various levels of RA at gastrula stages. Such treatments lead to development of embryos with loss of anterior structures. In addition, RA has a general effect on rhombomere morphology and specific effects on the development of the anterior rhombomeres. This effect is demonstrated using neurofilament antibodies, HRP staining and in situ hybridisation using a probe for expression of the Xenopus Krox-20 gene. Anatomically it is evident that the development of the hindbrain normally anterior to the otocyst (rhombomeres 1-4) is abnormal following RA treatment. Sensory and motor axons of cranial nerves V and VII form a single root and the peripheral paths of V and VII and IX and X are also abnormal, as is the more anterior location of the otocyst. These anatomical changes are accompanied by changes in the pattern of expression for the gene XKrox-20, which normally expresses in rhombomeres 3 and 5, but is found in a single band in the anterior hindbrain of treated embryos which standardly fail to generate the normal external segmental appearance. The results are discussed in terms of both the teratogenic and possible endogenous roles of RA during normal development of the central nervous system. We conclude that low doses of RA applied during gastrulation have specific effects on the anterior Xenopus hindbrain which appear to be evolutionarily conserved in the light of similar recent findings in zebrafish.
视黄酸是一种非常强效的致畸剂，也被认为是脊椎动物胚胎中的一种内源性发育信号分子。胚胎中一个可靠地受外源性视黄酸影响的区域是后脑。在本文中，我们详细描述了非洲爪蟾胚胎在原肠胚阶段用不同水平的视黄酸短暂处理后的后脑。这种处理导致胚胎发育时前部结构缺失。此外，视黄酸对菱脑节形态有普遍影响，对前部菱脑节的发育有特定影响。使用神经丝抗体、辣根过氧化物酶染色以及用非洲爪蟾Krox - 20基因表达探针进行原位杂交证明了这种影响。从解剖学上看，很明显，视黄酸处理后，正常情况下位于耳囊前方的后脑（菱脑节1 - 4）发育异常。三叉神经和面神经的感觉和运动轴突形成单一神经根，三叉神经、面神经以及舌咽神经和迷走神经的外周路径也异常，耳囊的位置也更靠前。这些解剖学变化伴随着XKrox - 20基因表达模式的改变，该基因通常在菱脑节3和5中表达，但在处理过的胚胎的后脑前部呈单条带出现，这些胚胎通常无法产生正常的外部节段外观。从视黄酸在中枢神经系统正常发育过程中的致畸作用和可能的内源性作用两个方面对结果进行了讨论。我们得出结论，原肠胚形成期间施加低剂量的视黄酸对非洲爪蟾后脑前部有特定影响，鉴于最近在斑马鱼中的类似发现，这些影响似乎在进化上是保守的。
