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

S. Y Christin Chong; Sheila S. Rosenberg; Stephen P J Fancy; Chao Zhao; Yun An A Shen; Angela T. Hahn; Aaron W. McGee; Xiaomei Xu; Binhai Zheng; Li I. Zhang; David H. Rowitch; Robin J M Franklin; Q. Richard Lu; Jonah R. Chan

doi:10.1073/pnas.1113540109

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

S. Y Christin Chong, Sheila S. Rosenberg, Stephen P J Fancy, Chao Zhao, Yun An A Shen, Angela T. Hahn, Aaron W. McGee, Xiaomei Xu, Binhai Zheng, Li I. Zhang, David H. Rowitch, Robin J M Franklin, Q. Richard Lu, Jonah R. Chan

Developmental Biology

Research output: Contribution to journal › Article › peer-review

179 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1299-1304
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	109
Issue number	4
DOIs	https://doi.org/10.1073/pnas.1113540109
State	Published - Jan 24 2012

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1113540109

Cite this

Chong, S. Y. C., Rosenberg, S. S., Fancy, S. P. J., Zhao, C., Shen, Y. A. A., Hahn, A. T., McGee, A. W., Xu, X., Zheng, B., Zhang, L. I., Rowitch, D. H., Franklin, R. J. M., Lu, Q. R., & Chan, J. R. (2012). Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. Proceedings of the National Academy of Sciences of the United States of America, 109(4), 1299-1304. https://doi.org/10.1073/pnas.1113540109

Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. / Chong, S. Y Christin; Rosenberg, Sheila S.; Fancy, Stephen P J et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 4, 24.01.2012, p. 1299-1304.

Research output: Contribution to journal › Article › peer-review

Chong, SYC, Rosenberg, SS, Fancy, SPJ, Zhao, C, Shen, YAA, Hahn, AT, McGee, AW, Xu, X, Zheng, B, Zhang, LI, Rowitch, DH, Franklin, RJM, Lu, QR & Chan, JR 2012, 'Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 4, pp. 1299-1304. https://doi.org/10.1073/pnas.1113540109

@article{04d351c86e1f4817a1b7f92ecb355054,

title = "Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination",

abstract = "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.",

author = "Chong, {S. Y Christin} and Rosenberg, {Sheila S.} and Fancy, {Stephen P J} and Chao Zhao and Shen, {Yun An A} and Hahn, {Angela T.} and McGee, {Aaron W.} and Xiaomei Xu and Binhai Zheng and Zhang, {Li I.} and Rowitch, {David H.} and Franklin, {Robin J M} and Lu, {Q. Richard} and Chan, {Jonah R.}",

year = "2012",

month = jan,

day = "24",

doi = "10.1073/pnas.1113540109",

language = "English (US)",

volume = "109",

pages = "1299--1304",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "4",

}

TY - JOUR

T1 - Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination

AU - Chong, S. Y Christin

AU - Rosenberg, Sheila S.

AU - Fancy, Stephen P J

AU - Zhao, Chao

AU - Shen, Yun An A

AU - Hahn, Angela T.

AU - McGee, Aaron W.

AU - Xu, Xiaomei

AU - Zheng, Binhai

AU - Zhang, Li I.

AU - Rowitch, David H.

AU - Franklin, Robin J M

AU - Lu, Q. Richard

AU - Chan, Jonah R.

PY - 2012/1/24

Y1 - 2012/1/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863012409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863012409&partnerID=8YFLogxK

U2 - 10.1073/pnas.1113540109

DO - 10.1073/pnas.1113540109

M3 - Article

C2 - 22160722

AN - SCOPUS:84863012409

SN - 0027-8424

VL - 109

SP - 1299

EP - 1304

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 4

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this