Developmental Expression of the Proteolipid Protein Gene in the Nervous System

Dickinson, Peter James (1995) Developmental Expression of the Proteolipid Protein Gene in the Nervous System. PhD thesis, University of Glasgow.

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Proteolipid protein (PLP) and DM-20 account for more than 50% of total myelin protein in the central nervous system (CNS) and are produced by alternative splicing of the primary pip transcript. While PLP is thought to contribute to the stability of the intraperiod line in CNS myelin, little is known about the function of DM-20. It has been suggested that DM- 20 may be involved in oligodendrocyte differentiation and survival. The present work confirmed that the marked upregulation of the pip gene, and change in transcript ratio from dm-20 to pip predominance, occurs around the time of onset of myelination. In separate areas where myelination commenced at different times, these changes were correlated with the "age" of myelination in that area, rather than the chronological age of the developing CNS as a whole. Using a combination of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry, both transcripts and product were shown to be present in the embryonic mouse spinal cord as early as embryonic day 12 (E12). This expression was linked to the oligodendrocyte progenitor lineage. The presence of DM-20 isoprotein in these oligodendrocyte progenitors challenges previous perceptions that pip gene expression occurs only in mature post-mitotic oligodendrocytes. These studies also support the hypothesis that oligodendrocytes originate in a discrete region of the ventral spinal cord. Pip and dm-20 transcripts were demonstrated in the sciatic nerve, cranial sympathetic trunk and cranial cervical ganglion in the peripheral nervous system (PNS) with dm-20 being the predominant message present. No developmental change in plp/dm-20 transcript ratio similar to that seen in the CNS was seen. Nerve transection studies in both sciatic nerves (PNS) and optic nerves (CNS) demonstrated selective downregulation of the pip isoform suggesting different regulatory mechanisms for the two isomers, with axonal factors being more important for pip. Pip gene expression was present in the olfactory nerve layer (ONL) of the olfactory bulb during both embryogenesis and postnatal life. Transcripts and protein were found to be exclusively dm-20 and were shown to be present in the olfactory nerve ensheathing cells of the ONL. The combination of these studies has added further evidence to support the theory of separate functions for the PLP and DM-20 isoproteins. Expression of the dm-20 isoform appears to be the default pathway in "non-myelin" environments with dramatic upregulation of the pip isoform during active myelination.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Ian Griffiths
Keywords: Genetics, Neurosciences
Date of Award: 1995
Depositing User: Enlighten Team
Unique ID: glathesis:1995-74881
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 15:42
Last Modified: 27 Sep 2019 15:42

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