Function of vitamin A in vertebrate embryonic development
Function of vitamin A in vertebrate embryonic development
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DOI：
10.1093/jn/131.3.705
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发表时间：
2001-03-01
影响因子：
4.2
通讯作者：
Zile, MH
中科院分区：
文献类型：
--
作者：
Zile, MH
分子生物学和视黄酸受体研究的进展对了解维生素A在脊椎动物发育过程中的作用作出了重大贡献。利用完全缺乏维生素A的禽类胚胎，对这种维生素在早期发育阶段的功能进行了检查，结果表明，维生素A的需求始于原始心脏、循环系统和后脑的形成。在这个关键时期缺乏维生素A会导致严重的畸形和早期胚胎死亡。在啮齿动物模型中，维生素A缺乏症可以针对妊娠后期，并记录了在更高级的发育阶段对维生素A的需求。维生素A缺乏的主要目标组织包括心脏、中枢神经系统及其衍生结构、循环系统、泌尿生殖系统和呼吸系统，以及头骨、骨骼和四肢的发育。这些异常在类视黄醇受体敲除的小鼠突变体中也很明显；它们揭示了维生素A在发育过程中的形态学和分子功能。视黄酸受体（RAR）与类视黄酸X受体(RXR) α是重要的类视黄酸受体转录因子，在发育过程中通过全反式视黄酸生理配体在基因水平上调节维生素A的功能。维甲酸的体内平衡是由发育调节的维生素A代谢酶系统维持的。妊娠早期维生素A营养不足可能导致一些儿科先天性异常。
Advances in molecular biology and retinoic acid receptor research have significantly contributed to the understanding of the role of vitamin A during vertebrate development. Examination of the function of this vitamin during very early developmental stages using the completely vitamin A-depleted avian embryo has revealed that the vitamin A requirement begins at the time of formation of the primitive heart, circulation and specification of hindbrain. The lack of vitamin A at this critical time results in gross abnormalities and early embryonic death. In rodent models, vitamin A deficiency can be targeted to later gestational windows and documents the need for vitamin A for more advanced stages of development. Major target tissues of Vitamin A deficiency include the heart, central nervous system and structures derived from it, the circulatory, urogenital and respiratory systems, and the development of skull, skeleton and limbs. These abnormalities are also evident in mice mutants from retinoid receptor knockouts; they have revealed both morphological and molecular aspects of vitamin A function during development. Retinoic acid receptors (RAR) in partnership with retinoid X receptor (RXR)alpha appear to be the important retinoid receptor transcription factors regulating vitamin A function at the gene level during development via the physiologic ligand all-trans-retinoic acid. Homeostasis of retinoic acid is maintained by developmentally regulated vitamin A metabolism enzyme systems. Inadequate vitamin A nutrition during early pregnancy may account for some pediatric congenital abnormalities.