Retinoic acid, RARs and early development.
Retinoic acid, RARs and early development.
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DOI：
10.1530/jme-22-0041
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发表时间：
2022-11-01
影响因子：
3.5
通讯作者：
Duester, Gregg
中科院分区：
文献类型：
--
作者：
Berenguer, Marie;Duester, Gregg
维生素A(视黄醇)是胚胎发育和成人健康的重要营养素。早期研究证实视黄酸(RA)是视黄醇的代谢物，但其重要性并不明显。后来，人们观察到RA处理脊椎动物胚胎对肢体发育有致畸作用。随后，核RA受体(RARs)的发现揭示了RA通过一种称为RA信号的过程在转录水平上直接控制基因的表达。这一重要发现导致了进一步的研究表明，RA和RARs是正常胚胎发育所必需的。在正常发育过程中RA功能的确定一直是具有挑战性的，因为RA功能获得研究往往导致与RAR或RA功能丧失研究相冲突的关于正常发育的结论。然而，遗传功能丧失研究已经确定了内源性RA/RAR的直接靶基因，这些基因是特定组织正常发育所必需的。因此，消除RARs或RA生成酶的遗传功能丧失研究有助于揭示RA信号对于许多器官和组织的正常早期发育是必需的，包括后脑、体轴、体节、脊髓、前肢、心脏和眼睛。
Vitamin A (retinol) is an important nutrient for embryonic development and adult health. Early studies identified retinoic acid (RA) as a metabolite of retinol, however its importance was not apparent. Later, it was observed that RA treatment of vertebrate embryos had teratogenic effects on limb development. Subsequently, the discovery of nuclear RA receptors (RARs) revealed that RA controls gene expression directly at the transcriptional level through a process referred to as RA signaling. This important discovery led to further studies demonstrating that RA and RARs are required for normal embryonic development. The determination of RA function during normal development has been challenging as RA gain-of-function studies often lead to conclusions about normal development that conflict with RAR or RA loss-of-function studies. However, genetic loss-of-function studies have identified direct target genes of endogenous RA/RAR that are required for normal development of specific tissues. Thus, genetic loss-of-function studies that eliminate RARs or RA-generating enzymes have been instrumental in revealing that RA signaling is required for normal early development of many organs and tissues, including the hindbrain, posterior body axis, somites, spinal cord, forelimbs, heart, and eye.
影响因子：
2.7
作者：
Sorrell MR;Waxman JS
通讯作者：
Waxman JS