Zhang Jinghua, Smith Deborah, Yamamoto Miyuki, Ma Lanhua, McCaffery Peter
E. Kennedy Shriver Center, University of Massachusetts Medical School, University of Massachusetts, Waltham, Massachusetts 02452, USA.
J Neurosci. 2003 Aug 20;23(20):7610-20. doi: 10.1523/JNEUROSCI.23-20-07610.2003.
One general function for retinoic acid (RA) is pattern organization in the CNS. This regulatory factor has an essential role in spinal cord motor neuron and early posterior hindbrain development. In the anterior CNS, however, there is only a limited number of foci of RA synthesis, and less attention has been placed on regions such as the anterior hindbrain where RA synthesizing enzymes are absent. This study shows that a rich source of RA lies around the hindbrain from the RA synthetic enzyme retinaldehyde dehydrogenase-2 (RALDH2) present in the surrounding meninges and mesenchyme by embryonic day 13. RALDH2 is not distributed uniformly throughout the meninges but is restricted to territories over the developing hindbrain, suggesting that RA signaling may be localized to those regions. Further regulation of RA signaling is provided by the presence of a RA sink in the form of the CYP26B1 RA catabolic enzyme expressed in deeper regions of the brain. As a guide to the neural anatomy of hindbrain RA signaling, we used a mouse transgenic for a lacZ reporter gene driven by a RA response element (RAREhsplacZ) to identify regions of RA signaling. This reporter mouse provides evidence that RA signaling in the hindbrain after embryonic day 13 occurs in the regions of the cerebellum and precerebellar system adjacent to sources of RA, including the inferior olive and the pontine nuclei.
视黄酸（RA）的一个一般功能是在中枢神经系统中进行模式组织。这种调节因子在脊髓运动神经元和后脑早期发育中起着至关重要的作用。然而，在前脑中枢神经系统中，RA合成的位点数量有限，像后脑前部这种缺乏RA合成酶的区域受到的关注较少。本研究表明，到胚胎第13天时，由于周围脑膜和间充质中存在RA合成酶视黄醛脱氢酶-2（RALDH2），后脑周围存在丰富的RA来源。RALDH2并非均匀分布于整个脑膜，而是局限于发育中的后脑区域，这表明RA信号可能定位于这些区域。在大脑深部区域表达的CYP26B1 RA分解代谢酶以RA汇的形式存在，进一步调节了RA信号。作为后脑RA信号神经解剖学的指南，我们使用了一种转基因小鼠，其带有由RA反应元件（RAREhsplacZ）驱动的lacZ报告基因，以识别RA信号区域。这种报告基因小鼠提供了证据，表明胚胎第13天后，后脑的RA信号出现在与RA来源相邻的小脑和小脑前系统区域，包括下橄榄核和脑桥核。
