Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination

被引:169
|
作者
Chong, S. Y. Christin [2 ,3 ,4 ,5 ]
Rosenberg, Sheila S. [4 ,5 ]
Fancy, Stephen P. J. [6 ,7 ,8 ]
Zhao, Chao [9 ,10 ]
Shen, Yun-An A. [2 ,3 ]
Hahn, Angela T. [2 ,3 ]
McGee, Aaron W. [11 ,12 ]
Xu, Xiaomei [1 ]
Zheng, Binhai [13 ]
Zhang, Li I. [5 ,14 ]
Rowitch, David H. [6 ,7 ,8 ]
Franklin, Robin J. M. [9 ,10 ]
Lu, Q. Richard [1 ]
Chan, Jonah R. [2 ,3 ,4 ,5 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA
[4] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
[5] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Neurosci Grad Program, Los Angeles, CA 90033 USA
[6] Univ Calif San Francisco, Eli & Edythe Broad Inst Stem Cell Res & Regenerat, Dept Pediat, San Francisco, CA 94143 USA
[7] Univ Calif San Francisco, Eli & Edythe Broad Inst Stem Cell Res & Regenerat, Dept Neurosurg, San Francisco, CA 94143 USA
[8] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[9] Univ Cambridge, MRC, Ctr Stem Cell Biol & Regenerat Med, Cambridge CB3 0ES, England
[10] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England
[11] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst,Dept Pediat, Los Angeles, CA 90027 USA
[12] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst,Dept Biol Sci, Los Angeles, CA 90027 USA
[13] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA
[14] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Physiol & Biophys, Los Angeles, CA 90033 USA
基金
美国国家卫生研究院;
关键词
CENTRAL-NERVOUS-SYSTEM; CNS; REMYELINATION; DIFFERENTIATION; REGENERATION; EXPRESSION; PATTERNS; DATABASE; BIOLOGY; MICE;
D O I
10.1073/pnas.1113540109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A requisite component of nervous system development is the achievement of cellular recognition and spatial segregation through competition-based refinement mechanisms. Competition for available axon space by myelinating oligodendrocytes ensures that all relevant CNS axons are myelinated properly. To ascertain the nature of this competition, we generated a transgenic mouse with sparsely labeled oligodendrocytes and establish that individual oligodendrocytes occupying similar axon tracts can greatly vary the number and lengths of their myelin internodes. Here we show that intercellular interactions between competing oligodendroglia influence the number and length of myelin internodes, referred to as myelinogenic potential, and identify the amino-terminal region of Nogo-A, expressed by oligodendroglia, as necessary and sufficient to inhibit this process. Exuberant and expansive myelination/remyelination is detected in the absence of Nogo during development and after demyelination, suggesting that spatial segregation and myelin extent is limited by microenvironmental inhibition. We demonstrate a unique physiological role for Nogo-A in the precise myelination of the developing CNS. Maximizing the myelinogenic potential of oligodendrocytes may offer an effective strategy for repair in future therapies for demyelination.
引用
收藏
页码:1299 / 1304
页数:6
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