QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Zhang, H. Articles by Miller, R. H. Search for Related Content PubMed PubMed Citation Articles by Zhang, H. Articles by Miller, R. H.

 Previous Article  |  Next Article 

Volume 16, Number 21, Issue of November 1, 1996 pp. 6886-6895
Copyright ©1996 Society for Neuroscience

Density-Dependent Feedback Inhibition of Oligodendrocyte Precursor Expansion

Received Feb. 13, 1996; revised Aug. 7, 1996; accepted Aug. 9, 1996.

Hong Zhang and Robert H. Miller

Department of Neuroscience, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

The myelin sheath in the vertebrate CNS is formed by oligodendrocytes. The number of oligodendrocytes in a mature axon tract must be sufficient to myelinate all appropriate axons. How the number of oligodendrocytes is matched to axonal requirements and whether such matching involves axon-oligodendrocyte signaling or intrinsic oligodendrocyte self-regulation are not clear.

Using a combination of in vitro analyses, we demonstrate that oligodendrocyte precursors closely regulate their numbers through interactions between adjacent precursors. In low-density rat spinal cord cultures, the number of oligodendrocyte lineage cells increases rapidly. The addition of large numbers of oligodendrocyte precursors substantially reduces precursor expansion and results in a normalization of oligodendrocyte lineage cell numbers in the cultures over time. Thus, the number of oligodendrocyte lineage cells that develop appears dependent on the density of oligodendrocyte lineage cells. This normalization of cell number is reflected in assays of clonal potential and proliferation. For example, precursors gave rise to fewer progeny and proliferated less at high density. Reduced precursor expansion at high density was not attributable to the depletion of growth factors. Cocultures of high and low densities did not inhibit precursor expansion in low-density cultures, suggesting the requirement for local cell-cell interactions. The inhibition of precursor expansion was cell-type-specific and dependent on the presence of oligodendrocyte lineage cells. We propose that this density-dependent feedback inhibition of oligodendrocyte precursor expansion may play a primary role in regulating the number of oligodendrocytes in the developing spinal cord.

Key words: spinal cord; oligodendrocyte precursors; cell proliferation; retroviral analysis; density dependence

This article has been cited by other articles:

				S. S. Rosenberg, E. E. Kelland, E. Tokar, A. R. De La Torre, and J. R. Chan From the Cover: The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation PNAS, September 23, 2008; 105(38): 14662 - 14667. [Abstract] [Full Text] [PDF]

				S. Herculano-Houzel, C. E. Collins, P. Wong, and J. H. Kaas Cellular scaling rules for primate brains PNAS, February 27, 2007; 104(9): 3562 - 3567. [Abstract] [Full Text] [PDF]

				S. Herculano-Houzel, B. Mota, and R. Lent Cellular scaling rules for rodent brains PNAS, August 8, 2006; 103(32): 12138 - 12143. [Abstract] [Full Text] [PDF]

				H.-H. Tsai, W. B. Macklin, and R. H. Miller Netrin-1 Is Required for the Normal Development of Spinal Cord Oligodendrocytes J. Neurosci., February 15, 2006; 26(7): 1913 - 1922. [Abstract] [Full Text] [PDF]

				S. Genoud, C. Lappe-Siefke, S. Goebbels, F. Radtke, M. Aguet, S. S. Scherer, U. Suter, K.-A. Nave, and N. Mantei Notch1 control of oligodendrocyte differentiation in the spinal cord J. Cell Biol., August 19, 2002; 158(4): 709 - 718. [Abstract] [Full Text] [PDF]

				B. A. Barres and M. C. Raff Axonal Control of Oligodendrocyte Development J. Cell Biol., December 13, 1999; 147(6): 1123 - 1128. [Abstract] [Full Text] [PDF]

				H. Ueda, J.M. Levine, R.H. Miller, and B.D. Trapp Rat Optic Nerve Oligodendrocytes Develop in the Absence of Viable Retinal Ganglion Cell Axons J. Cell Biol., September 20, 1999; 146(6): 1365 - 1374. [Abstract] [Full Text] [PDF]

				X Yuan, A. Eisen, C. McBain, and V Gallo A role for glutamate and its receptors in the regulation of oligodendrocyte development in cerebellar tissue slices Development, January 8, 1998; 125(15): 2901 - 2914. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help