Jacobs Sharoni, Lie D Chichung, DeCicco Kathleen L, Shi Yanhong, DeLuca Luigi M, Gage Fred H, Evans Ronald M
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3902-7. doi: 10.1073/pnas.0511294103. Epub 2006 Feb 27.
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 SREBP1c as well as components of the Wnt signaling pathway. Our results reveal RA as a crucial contributor to early stages of adult neurogenesis and survival in vivo.
维甲酸（RA）通常在体外用于将包括成体神经干细胞在内的干细胞群体分化为神经元；然而，RA在成体神经发生过程中的体内功能在很大程度上仍未得到探索。我们发现，成年小鼠体内RA的耗竭会导致齿状回颗粒细胞层内神经元分化显著减少。RA对神经发生的作用发生在早期，因为RA缺乏也会导致表达未成熟神经元标志物的新生细胞减少。此外，虽然在缺乏RA的情况下增殖不受影响，但细胞存活率显著降低。最后，一项针对类视黄醇诱导基因的筛选确定了代谢靶点，包括脂质转运蛋白CD-36和ABCA-1、脂肪生成主调节因子SREBP1c以及Wnt信号通路的成分。我们的结果表明，RA是成体神经发生早期阶段和体内细胞存活的关键促成因素。
