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The Journal of Neuroscience, September 27, 2006, 26(39):9881-9891; doi:10.1523/JNEUROSCI.2246-06.2006

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Cellular/Molecular
Identification of a Novel Oligodendrocyte Cell Adhesion Protein Using Gene Expression Profiling

Joseph A. Nielsen,¹ Dragan Maric,² Pierre Lau,¹ Jeffery L. Barker,² and Lynn D. Hudson¹

¹Section of Developmental Genetics, ²Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892

Correspondence should be addressed to Lynn D. Hudson, Building 49, Room 5A82, 49 Convent Drive, Bethesda, MD 20892-4479. Email: hudsonl1{at}od.nih.gov

Oligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the molecular mechanisms underlying this transformation, we performed a comparative analysis using gene expression profiling of A2B5⁺ oligodendrocyte progenitors and O4⁺ oligodendrocytes. Cells were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using Affymetrix microarrays, 1707 transcripts were identified with a more than twofold increase in expression in O4⁺ oligodendrocytes. Many genes required for oligodendrocyte differentiation were upregulated in O4⁺ oligodendrocytes, including numerous genes encoding myelin proteins. Transcriptional changes included genes required for cell adhesion, actin cytoskeleton regulation, and fatty acid and cholesterol biosynthesis. At the O4⁺ stage, there was an increase in expression of a novel proline-rich transmembrane protein (Prmp). Localized to the plasma membrane, Prmp displays adhesive properties that may be important for linking the extracellular matrix to the actin cytoskeleton. Together, our results highlight the usefulness of this discovery-driven experimental strategy to identify genes relevant to oligodendrocyte differentiation and myelination.

Key words: oligodendrocyte; microarray; myelination; adhesion; cytoskeleton; actin

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Received May 26, 2006; revised Aug. 16, 2006; accepted Aug. 20, 2006.

Correspondence should be addressed to Lynn D. Hudson, Building 49, Room 5A82, 49 Convent Drive, Bethesda, MD 20892-4479. Email: hudsonl1{at}od.nih.gov

This article has been cited by other articles:

				P. Lau, J. D. Verrier, J. A. Nielsen, K. R. Johnson, L. Notterpek, and L. D. Hudson Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes J. Neurosci., November 5, 2008; 28(45): 11720 - 11730. [Abstract] [Full Text] [PDF]

				A Lehotzky, N Tokesi, I Gonzalez-Alvarez, V Merino, M Bermejo, F Orosz, P Lau, G.G Kovacs, and J Ovadi Progress in the development of early diagnosis and a drug with unique pharmacology to improve cancer therapy Phil Trans R Soc A, October 13, 2008; 366(1880): 3599 - 3617. [Abstract] [Full Text] [PDF]

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