A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions

	A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions
	Dai, WX; Nian, XM; Zhou, ZH; Du, AL; Liu, Q; Jia, SF; Lu, Y; Li, DP; Lu, XY; Zhu, YQ; Huang, QY; Lu, JQ; Xiao, YS; Zheng, LK; Lei, WY; Sheng, NY; Zang, XJ; Hou, YQ; Qiu, ZL; Xu, R; Xu, SH; Zhang, XQ; Zhang, L
	2025
发表期刊	Cell Reports
ISSN	2211-1247
卷号	44 期号:4
摘要	Oligodendrocyte maturation arrest in hypoxia-induced white matter injury (WMI) results in long-term neurofunctional disabilities of preterm infants. Although neurons are closely linked to myelination regulation, how neurons respond to the above process remains elusive. Here, we identify a compensatory role of neuronal Slit1-dependent signaling in protecting against hypoxia-induced hypomyelination and ameliorating motor and cognitive disabilities. Conditional ablation of Slit1 in neurons exacerbates hypoxia-induced hypomyelination but is negligible for developmental myelination. Secreted Slit1 from hypoxic neurons directly targets oligodendrocyte, acting through Robo2-srGAP1-RhoA signaling. Pharmacological inhibition of RhoA restores myelination and promotes neurofunctional recovery in adolescent mice. Notably, natural selection analysis and functional validation indicate an adaptive variant with higher Slit1 gene expression in the Tibetan population, which has low oxygen availability. Collectively, these findings show a neuronal Slit1-dependent program of OL differentiation and suggest that targeting the Slit1-Robo2 signaling axis may have therapeutic potential for treatment of preterm infants with hypoxic WMI.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14963
专题	科研部门_神经突触机制与功能研究组（盛能印）
推荐引用方式 GB/T 7714	Dai, WX,Nian, XM,Zhou, ZH,et al. A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions[J]. Cell Reports,2025,44(4).
APA	Dai, WX.,Nian, XM.,Zhou, ZH.,Du, AL.,Liu, Q.,...&Zhang, L.(2025).A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions.Cell Reports,44(4).
MLA	Dai, WX,et al."A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions".Cell Reports 44.4(2025).

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