Regular Article
PDGF-α Receptor and Myelin Basic Protein mRNAs Are Not Coexpressed by Oligodendrocytesin Vivo:A Doublein SituHybridization Study in the Anterior Medullary Velum of the Neonatal Rat

https://doi.org/10.1006/mcne.1996.0590Get rights and content

Abstract

Platelet-derived growth factor (PDGF) is a growth-regulatory dimer with A and B subunits. PDGF-AA, acting via PDGF receptors of the α-unit subtype (PDGF-αR), is implicated in the differentiation of oligodendrocyte precursors and in the survival of newly formed oligodendrocytes, which gradually lose expression of PDGF-αR. However, it is unclear whether terminally differentiated oligodendrocytes express PDGF-αRin vivo.To address this question, and to help clarify the role of PDGF-AA in late oligodendrocyte differentiation, we have used doublein situhybridization with digoxigenin- and fluorescein-labeled riboprobes to relate PDGF-αR mRNA and myelin basic protein (MBP) mRNA expression in the isolated intact anterior medullary velum (AMV) of rats ages Postnatal Day (P) 10–12 and P30–32. In parallel experiments, AMV were immunolabeled with the oligodendrocyte-specific monoclonal antibody Rip to provide information on oligodendrocyte development and the extent of myelination. At P10, the AMV contained tracts in which axons ranged from unmyelinated to fully myelinated, whereas myelination was complete in P30–32 AMV. The first oligodendrocytes to express MBP mRNA or Rip were promyelinating oligodendrocytes, which had a “star-burst” morphology and had not yet begun to form myelin sheaths. As myelination proceeded, MBP mRNA became dispersed throughout oligodendrocyte units, comprising cell somata, processes, and internodal myelin sheaths. By P30–32, MBP mRNA had been redistributed to the myelin sheaths only, reflecting a change in the site of protein synthesis in mature myelinated axon tracts. At no stage of oligodendrocyte differentiation did we observe cellular coexpression of mRNA for PDGFαR and MBP. Our results indicated that oligodendrocytes lost the expression of PDGFαR prior to gaining that of myelin gene products, and preclude an action of PDGF-AA on Rip+/MBP+star-burst promyelinating oligodendrocytes. The spatial and temporal expression of PDGF-αR mRNA in the AMV was inversely related to the pattern of maturation of both myelin and oligodendrocytes, and is consistent with PDGF-αR being expressed by pro-oligodendrocytes. A notable finding was the high level of expression of PDGF-αR mRNA in the AMV of juvenile rats, localized to cell bodies within the myelinated axon tracts, strongly suggesting that oligodendrocyte precursors persisted in the mature velum.

References (50)

  • H.-J. Yeh et al.

    PDGF A-chain gene is expressed by mammalian neurons during development and in maturity

    Cell

    (1991)
  • W.-P. Yu et al.

    Embryonic expression of myelin genes: Evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neurol tube

    Neuron

    (1994)
  • R.C. Armstrong et al.

    Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules

    J. Neurosci. Res.

    (1990)
  • B.A. Barres et al.

    Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons

    Nature

    (1993)
  • B.A. Barres et al.

    Multiple extracellular signals are required for long-term oligodendrocyte survival

    Development

    (1993)
  • M. Berry et al.

    Axon–glial relationships in the anterior medullary velum of the adult rat

    J. Neurocytol.

    (1995)
  • A.M. Butt et al.

    Biochemical subtypes of oligodendrocyte in the anterior medullary velum of the rat as revealed by the monoclonal antibody Rip

    Glia

    (1995)
  • A.M. Butt et al.

    Oligodendrocyte development and myelination in the anterior medullary velum of the rat brain

    J. Neurocytol.

    (1997)
  • A.T. Campagnoni et al.

    Post-transcriptional regulation of myelin protein gene expression

    Ann. N. Y. Acad. Sci.

    (1991)
  • M. Dubois-Dalcq et al.

    Emergence of three myelin proteins in oligodendrocytes cultured without neurons

    J. Cell Biol.

    (1986)
  • E. Dutly et al.

    Neurons and astrocytes influence the development of purified O-2A progenitor cells

    Glia

    (1991)
  • J. Ellison et al.

    Platelet derived growth factor receptor is expressed by cells in the early oligodendrocyte lineage

    J. Neurosci. Res.

    (1994)
  • J.A. Ellison et al.

    Amoeboid microglia expressing GD3 ganglioside are concentrated in regions of oligodendrogenesis during development of the rat corpus callosum

    Glia

    (1995)
  • B. Friedman et al.

    In situ demonstration of mature oligodendrocytes and their processes: An immunocytochemical study with a new monoclonal antibody, Rip

    Glia

    (1989)
  • Cited by (40)

    • The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties: Implications for Regenerative Medicine

      2018, American Journal of Pathology
      Citation Excerpt :

      Of the PDGF family, PDGF-AA is most known for its functions in OL development. PDGF-AA binds to the PDGFα receptor that is expressed by many OL progenitors.91 Mice lacking PDGFα receptors demonstrate defects in OL progenitor proliferation and migration and show precocious OL differentiation and myelination.92,93

    • Oligodendrocyte progenitor cells are paired with GABA neurons in the mouse dorsal cortex: Unbiased stereological analysis

      2017, Neuroscience
      Citation Excerpt :

      These estimates suggest that the stereological parameters chosen were appropriate (Gundersen et al., 1999). PDGFRα is selectively expressed by OPCs (Nishiyama et al., 1996; Butt et al., 1997). To determine the total number of OPCs in the dorsal portion of the cerebral cortex of adult mice, we looked at the estimated total number of PDGFRα+ cells located between lateral 0.36 mm and lateral 2.52 mm in those regions.

    • Unbiased stereological analysis of the fate of oligodendrocyte progenitor cells in the adult mouse brain and effect of reference memory training

      2017, Behavioural Brain Research
      Citation Excerpt :

      Oligodendrocyte progenitor cells (OPCs; also known as NG2-glial cells, synantocytes, or polydendrocytes) are a type of glial cell that give rise, as their name suggests, to myelinating oligodendrocytes during early stages of post-natal life [1,2]. OPCs specifically express the platelet-derived growth factor receptor alpha (PDGFRα) and the chondroitin sulfate proteoglycan neuron-glia antigen 2 (NG2), both of which are downregulated in favor of O4 and myelin-specific antigens as the cell transitions from an OPC to an oligodendrocyte phenotype [3–6]. Interestingly, a large number of OPCs remain undifferentiated after developmental myelination is completed, and OPCs correspond to 2–9% of the total cell population of the adult brain [7–11].

    • Dysfunction of platelet-derived growth factor receptor α (PDGFRα) represses the production of oligodendrocytes from arylsulfatase A-deficient multipotential neural precursor cells

      2015, Journal of Biological Chemistry
      Citation Excerpt :

      Because the PDGFRα is a critical signal for the generation of OPCs and their timely maturation into OLs, we studied its expression in ASA−/− NPs. PDGFRα is crucial for regulating the number and survival of OPCs/OL during myelination (9–11, 39–41), mainly by regulating the activity of the AKT or ERK1/2 pathway (42–44). To determine whether this receptor was involved in the phenotype of ASA−/− cells, various experiments were performed.

    • Oligodendrocyte morphology

      2009, Encyclopedia of Neuroscience
    View all citing articles on Scopus
    View full text