Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer.
Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer.
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DOI：
10.1038/s41467-023-40486-5
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发表时间：
2023-08-11
影响因子：
16.6
通讯作者：
Poss, Kenneth D. D.
中科院分区：
文献类型：
--
作者：
Cigliola, Valentina;Shoffner, Adam;Lee, Nutishia;Ou, Jianhong;Gonzalez, Trevor J. J.;Hoque, Jiaul;Becker, Clayton J. J.;Han, Yanchao;Shen, Grace;Faw, Timothy D. D.;Abd-El-Barr, Muhammad M. M.;Varghese, Shyni;Asokan, Aravind;Poss, Kenneth D. D.
与成年哺乳动物不同，斑马鱼在瘫痪损伤后可以再生脊髓组织并恢复运动能力。在这里，我们发现斑马鱼脊髓的室管膜细胞在横断损伤时产生神经源性因子Hb-egfa。携带hb-egfa突变的动物在脊髓横断后表现出游泳能力、轴突交叉和组织桥接缺陷，并与神经元生成指标中断相关。局部重组人HB-EGF递送改变室管膜细胞循环和组织桥接，增强功能再生。表观遗传学分析揭示了与hb-egfa相关的组织再生增强因子（TREE）在脊髓损伤中指导基因表达。系统递送含有该斑马鱼TREE靶基因表达的重组aav来粉碎新生小鼠脊髓损伤，而不是成年小鼠脊髓损伤。此外，通过AAV给药以增强剂为基础的HB-EGF递送可改善新生儿脊髓挤压损伤后的轴突密度。我们的研究结果确定Hb-egf是先天脊髓再生所必需的神经源性因子，并提出了改善哺乳动物脊髓修复的策略。与哺乳动物不同，斑马鱼在脊椎瘫痪后可以再生并恢复运动能力。本文作者表明，神经源性因子Hb-egf促进斑马鱼的脊髓再生，并受到一种增强子的调节，这种增强子在新生小鼠的促再生环境中也能类似地直接表达。
Unlike adult mammals, zebrafish regenerate spinal cord tissue and recover locomotor ability after a paralyzing injury. Here, we find that ependymal cells in zebrafish spinal cords produce the neurogenic factor Hb-egfa upon transection injury. Animals with hb-egfa mutations display defective swim capacity, axon crossing, and tissue bridging after spinal cord transection, associated with disrupted indicators of neuron production. Local recombinant human HB-EGF delivery alters ependymal cell cycling and tissue bridging, enhancing functional regeneration. Epigenetic profiling reveals a tissue regeneration enhancer element (TREE) linked to hb-egfa that directs gene expression in spinal cord injuries. Systemically delivered recombinant AAVs containing this zebrafish TREE target gene expression to crush injuries of neonatal, but not adult, murine spinal cords. Moreover, enhancer-based HB-EGF delivery by AAV administration improves axon densities after crush injury in neonatal cords. Our results identify Hb-egf as a neurogenic factor necessary for innate spinal cord regeneration and suggest strategies to improve spinal cord repair in mammals. Zebrafish can regenerate after paralyzing spine injuries and regain locomotor ability, unlike mammals. Here authors show that the neurogenic factor Hb-egf promotes spinal cord regeneration in zebrafish and is regulated by an enhancer that can similarly direct expression in the pro-regenerative setting of neonatal mice.
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血清素促进斑马鱼脊髓运动神经元的发育和再生。
影响因子：
8.8
作者：
Barreiro-Iglesias A;Mysiak KS;Scott AL;Reimer MM;Yang Y;Becker CG;Becker T
通讯作者：
Becker T
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Dias DO;Kim H;Holl D;Werne Solnestam B;Lundeberg J;Carlén M;Göritz C;Frisén J
通讯作者：
Frisén J
影响因子：
3.6
作者：
Goldshmit Y;Tang JKKY;Siegel AL;Nguyen PD;Kaslin J;Currie PD;Jusuf PR
通讯作者：
Jusuf PR
影响因子：
11.8
作者：
Goldman JA;Kuzu G;Lee N;Karasik J;Gemberling M;Foglia MJ;Karra R;Dickson AL;Sun F;Tolstorukov MY;Poss KD
通讯作者：
Poss KD