Department of Neurology,
Department of Neurology.
J Neurosci. 2020 Mar 4;40(10):2015-2024. doi: 10.1523/JNEUROSCI.2249-19.2020. Epub 2020 Jan 27.
Neural stem cells (NSCs) persist throughout life in the subventricular zone (SVZ) neurogenic niche of the lateral ventricles as Type B1 cells in adult mice. Maintaining this population of NSCs depends on the balance between quiescence and self-renewing or self-depleting cell divisions. Interactions between B1 cells and the surrounding niche are important in regulating this balance, but the mechanisms governing these processes have not been fully elucidated. The cytoplasmic FMRP-interacting protein (Cyfip1) regulates apical-basal polarity in the embryonic brain. Loss of Cyfip1 during embryonic development in mice disrupts the embryonic niche and affects cortical neurogenesis. However, a direct role for Cyfip1 in the regulation of adult NSCs has not been established. Here, we demonstrate that Cyfip1 expression is preferentially localized to B1 cells in the adult mouse SVZ. Loss of in the embryonic mouse brain results in altered adult SVZ architecture and expansion of the adult B1 cell population at the ventricular surface. Furthermore, acute deletion of in adult NSCs results in a rapid change in adherens junction proteins as well as increased proliferation and number of B1 cells at the ventricular surface. Together, these data indicate that Cyfip1 plays a critical role in the formation and maintenance of the adult SVZ niche; furthermore, deletion of unleashes the capacity of adult B1 cells for symmetric renewal to increase the adult NSC pool. Neural stem cells (NSCs) persist in the subventricular zone of the lateral ventricles in adult mammals, and the size of this population is determined by the balance between quiescence and self-depleting or renewing cell division. The mechanisms regulating these processes are not fully understood. This study establishes that the cytoplasmic FMRP interacting protein 1 (Cyfip1) regulates NSC fate decisions in the adult subventricular zone and adult NSCs that are quiescent or typically undergo self-depleting divisions retain the ability to self-renew. These results contribute to our understanding of how adult NSCs are regulated throughout life and has potential implications for human brain disorders.
神经干细胞 (NSCs) 作为成年小鼠脑室下区 (SVZ) 神经发生龛中的 B1 型细胞，终生存在。维持这一 NSCs 群体取决于静止和自我更新或自我消耗的细胞分裂之间的平衡。B1 细胞与周围龛之间的相互作用对于调节这种平衡很重要，但调节这些过程的机制尚未完全阐明。细胞质 FMRP 相互作用蛋白 (Cyfip1) 在胚胎大脑中调节顶端-基底极性。在小鼠胚胎发育过程中丢失 Cyfip1 会破坏胚胎龛并影响皮质神经发生。然而，Cyfip1 在调节成年 NSCs 中的直接作用尚未确定。在这里，我们证明 Cyfip1 表达在成年小鼠 SVZ 中优先定位于 B1 细胞。在胚胎期敲除 会导致成年 SVZ 结构改变，脑室面的成年 B1 细胞群体扩大。此外，在成年 NSCs 中急性删除 会导致黏着连接蛋白发生快速变化，以及脑室面的 B1 细胞增殖和数量增加。总之，这些数据表明 Cyfip1 在成年 SVZ 龛的形成和维持中发挥关键作用；此外，删除 会释放成年 B1 细胞进行对称更新的能力，从而增加成年 NSC 池。神经干细胞 (NSCs) 存在于成年哺乳动物的侧脑室室下区，其大小取决于静止和自我消耗或更新细胞分裂之间的平衡。调节这些过程的机制尚不完全清楚。本研究确立了细胞质 FMRP 相互作用蛋白 1 (Cyfip1) 调节成年 SVZ 中的 NSC 命运决定，并且静止或通常经历自我消耗分裂的成年 NSCs 保留自我更新的能力。这些结果有助于我们了解 NSCs 如何在整个生命周期中受到调节，并可能对人类大脑疾病产生影响。
