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Maintenance of the relative proportion of oligodendrocytes to axons even in the absence of BAX and BAK

Authors

  • Kumi Kawai,

    1. Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
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    • *

      K.K. and T.I. contributed equally to this work.

  • Takayuki Itoh,

    1. Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
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    • *

      K.K. and T.I. contributed equally to this work.

  • Aki Itoh,

    1. Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
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  • Makoto Horiuchi,

    1. Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
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  • Kouji Wakayama,

    1. Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
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  • Peter Bannerman,

    1. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
    2. Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA, USA
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  • James Y. Garbern,

    1. Department of Neurology and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA
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  • David Pleasure,

    1. Department of Neurology, University of California Davis, School of Medicine, Sacramento, CA, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, CA, USA
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  • Tullia Lindsten

    1. Department of Pathology and Laboratory Medicine, and Abramson Family Cancer Research Institute, The University of Pennsylvania, Philadelphia, PA, USA
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Dr T. Itoh, 601A Shriners Hospitals for Children Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817, USA.
E-mail: takito@ucdavis.edu

Abstract

Highly purified oligodendroglial lineage cells from mice lacking functional bax and bak genes were resistant to apoptosis after in-vitro differentiation, indicating an essential role of the intrinsic apoptotic pathway in apoptosis of oligodendrocytes in the absence of neurons (axons) and other glial cells. These mice therefore provide a valuable tool with which to evaluate the significance of the intrinsic apoptotic pathway in regulating the population sizes of oligodendrocytes and oligodendroglial progenitor cells. Quantitative analysis of the optic nerves and the dorsal columns of the spinal cord revealed that the absolute numbers of mature oligodendrocytes immunolabeled for aspartoacylase and adult glial progenitor cells expressing NG2 chondroitin sulfate proteoglycan were increased in both white matter tracts of adult bax/bak-deficient mice and, to a lesser extent, bax-deficient mice, except that there was no increase in NG2-positive progenitor cells in the dorsal columns of these strains of mutant mice. These increases in mature oligodendrocytes and progenitor cells in bax/bak-deficient mice were unexpectedly proportional to increases in numbers of axons in these white matter tracts, thus retaining the oligodendroglial lineage to axon ratios of at most 1.3-fold of the physiological numbers. This is in contrast to the prominent expansion in numbers of neural precursor cells in the subventricular zones of these adult mutant mice. Our study indicates that homeostatic control of cell number is different for progenitors of the oligodendroglial and neuronal lineages. Furthermore, regulatory mechanism(s) operating in addition to apoptotic elimination through the intrinsic pathway, appear to prevent the overproduction of highly mitotic oligodendroglial progenitor cells.

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