少突胶质细胞
生物
血清反应因子
髓鞘
细胞生物学
细胞骨架
肌动蛋白
肌动蛋白细胞骨架
转录因子
神经科学
细胞
基因
遗传学
中枢神经系统
作者
Tal Iram,Miguel Ángel García,Jérémy Amand,Achint Kaur,Manasi Iyer,Mable Lam,Nicholas Ambiel,Andreas Keller,Tony Wyss‐Coray,Fabian Kern,J. Bradley Zuchero
标识
DOI:10.1101/2022.09.21.508765
摘要
ABSTRACT Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease. Highlights Developmental CNS myelination requires the transcription factor SRF in oligodendrocytes. SRF targets actin and actin-regulatory but not myelin related genes. SRF drives oligodendrocyte actin cytoskeleton dynamics during early stages of myelination.
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