Instituto Cajal, CSIC, 28002 Madrid, Spain.
Instituto de Biomedicina de Valencia, CSIC, 46010 Valencia, Spain.
Cell Rep. 2022 Feb 1;38(5):110313. doi: 10.1016/j.celrep.2022.110313.
The adult neurogenic niche in the hippocampus is maintained through activation of reversibly quiescent neural stem cells (NSCs) with radial glia-like morphology (RGLs). Here, we show that the expression of SoxD transcription factors Sox5 and Sox6 is enriched in activated RGLs. Using inducible deletion of Sox5 or Sox6 in the adult mouse brain, we show that both genes are required for RGL activation and the generation of new neurons. Conversely, Sox5 overexpression in cultured NSCs interferes with entry in quiescence. Mechanistically, expression of the proneural protein Ascl1 (a key RGL regulator) is severely downregulated in SoxD-deficient RGLs, and Ascl1 transcription relies on conserved Sox motifs. Additionally, loss of Sox5 hinders the RGL activation driven by neurogenic stimuli such as environmental enrichment. Altogether, our data suggest that SoxD genes are key mediators in the transition of adult RGLs from quiescence to an activated mitotic state under physiological situations.
海马体中的成人神经发生龛通过激活具有放射状胶质样形态（RGL）的可逆静止神经干细胞（NSC）来维持。在这里，我们表明转录因子 SoxD 的 Sox5 和 Sox6 表达丰富于激活的 RGL 中。使用诱导型删除成年小鼠大脑中的 Sox5 或 Sox6，我们表明这两个基因对于 RGL 激活和新神经元的产生都是必需的。相反，在培养的 NSCs 中过表达 Sox5 会干扰其进入静止状态。从机制上讲，在 SoxD 缺陷型 RGL 中，原神经蛋白 Ascl1（RGL 的关键调节因子）的表达严重下调，并且 Ascl1 转录依赖于保守的 Sox 基序。此外，Sox5 的缺失会阻碍环境富集等神经发生刺激驱动的 RGL 激活。总之，我们的数据表明 SoxD 基因是成人 RGL 在生理情况下从静止状态向激活有丝分裂状态过渡的关键介质。
