Retinoic acid is required early during adult neurogenesis in the dentate gyrus
Retinoic acid is required early during adult neurogenesis in the dentate gyrus
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DOI：
10.1073/pnas.0511294103
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发表时间：
2006-03-07
影响因子：
11.1
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Jacobs, S;Lie, DC;Evans, RM
维甲酸（RA）通常在体外用于将干细胞群（包括成体神经干细胞）分化成神经元;然而，RA在成体神经发生期间的体内功能在很大程度上仍未被探索。我们发现，在成年小鼠的RA耗竭导致齿状回的颗粒细胞层内的神经元分化显着降低。RA对神经发生的贡献发生在早期，因为RA缺乏也导致表达未成熟神经元标记物的新生细胞减少。此外，虽然在RA不存在期间增殖不受影响，但细胞存活率显著降低。最后，筛选类维生素A诱导的基因鉴定了代谢靶点，包括脂质转运蛋白CD-36和ABCA-1，脂肪生成主调节因子SREIBP 1c以及Writ信号通路的组分。我们的研究结果表明，RA作为一个重要的贡献者的早期阶段的成年神经发生和生存在体内。
Retinoic acid (RA) is commonly used in vitro to differentiate stem cell populations including adult neural stem cells into neurons; however, the in vivo function of RA during adult neurogenesis remains largely unexplored. We found that depletion of RA in adult mice leads to significantly decreased neuronal differentiation within the granular cell layer of the dentate gyrus. RA contribution to neurogenesis occurs early, for RA deficiency also results in a decrease in newborn cells expressing an immature neuronal marker. Furthermore, although proliferation is unaffected during RA absence, cell survival is significantly reduced. Finally, a screen for retinoid-induced genes identifies metabolic targets including the lipid transporters, CD-36 and ABCA-1, the lipogenic master regulator SREIBP1c as well as components of the Writ signaling pathway. Our results reveal RA as a crucial contributor to early stages of adult neurogenesis and survival in vivo.