Sanford-Burnham Medical Research Institute, Development and Aging Program, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Semin Cell Dev Biol. 2013 Dec;24(10-12):694-700. doi: 10.1016/j.semcdb.2013.08.001. Epub 2013 Aug 21.
The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA receptors that control differentiation of progenitor cells important for vertebrate development. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function. RA first begins to act during early organogenesis when RA generated in trunk mesoderm begins to function as a diffusible signal controlling progenitor cell differentiation. In neuroectoderm, RA functions as an instructive signal to stimulate neuronal differentiation of progenitor cells in the hindbrain and spinal cord. RA is not required for early neuronal differentiation of the forebrain, but at later stages RA stimulates neuronal differentiation in forebrain basal ganglia. RA also acts as a permissive signal for differentiation by repressing fibroblast growth factor (FGF) signaling in differentiated cells as they emerge from progenitor populations in the caudal progenitor zone and second heart field. In addition, RA signaling stimulates differentiation of spermatogonial germ cells and induces meiosis in male but not female gonads. A more complete understanding of the normal functions of RA signaling during development will guide efforts to use RA as a differentiation agent for therapeutic purposes.
维生素 A 代谢产物视黄酸 (RA) 作为核 RA 受体的配体，控制着脊椎动物发育中祖细胞的分化。缺乏生成 RA 的酶的小鼠胚胎的遗传研究对于解析 RA 功能非常重要。RA 首先在早期器官发生时开始起作用，此时躯干中胚层生成的 RA 开始作为一种扩散信号，控制祖细胞的分化。在神经外胚层中，RA 作为一种指导信号，刺激后脑和脊髓中祖细胞的神经元分化。RA 对于前脑的早期神经元分化不是必需的，但在后期，RA 刺激前脑基底神经节的神经元分化。RA 还通过抑制从尾部祖细胞区和第二心区的祖细胞群体中出现的分化细胞中的成纤维细胞生长因子 (FGF) 信号，作为分化的许可信号。此外，RA 信号刺激精原细胞生殖细胞的分化，并诱导雄性而不是雌性性腺中的减数分裂。更全面地了解 RA 信号在发育过程中的正常功能将指导我们努力将 RA 用作治疗目的的分化剂。
