<i>Plp</i> Gene Regulation in the Developing Murine Optic Nerve: Correlation with Oligodendroglial Process Alignment along the Axons

Abstract

The factors regulating the expression and splicing of the major myelin gene, proteolipid protein (Plp), are unclear. The gene encodes two splice variants, Plp and Dm20. During active myelination, transcription of the Plp gene is markedly upregulated and the splice variant ratio becomes Plp-mRNA dominant. We hypothesised that these aspects of Plp gene regulation are linked to overt axonal contact. Using the developing optic nerve of mice, we demonstrate that alignment of oligodendroglial processes with the axon correlates with both the expression of Plp-mRNA and the transcriptional upregulation of the gene. We test the above hypothesis more extensively in a subsequent study.

Focal adhesion kinase (FAK): A regulator of CNS myelination

“…Due to the region-specific timing of active myelination in the CNS, however, individual knock-out, i.e. tamoxifen injection, strategies need to be employed for specific CNS regions (Caley and Maxwell 1968; Foran and Peterson 1992; Leone et al 2003; Thomson et al 2005). …”

“…For the studies presented here, we chose the optic nerve as the anatomical region of interest due to its relatively simple morphology and the well described chronology of oligodendrocyte differentiation and myelination (Butt and Ransom, 1993; Colello et al, 1995; Hildebrand and Waxman, 1984; Hunter and Bedi, 1986; Skoff et al, 1976a; Skoff et al, 1976b; Skoff et al, 1980; Tennekoon et al, 1977; Thomson et al, 2005). In the optic nerve of developing C57Bl/6 mice, i.e.…”

“…In the optic nerve of developing C57Bl/6 mice, i.e. animals of genetic background similar to the one of the Fak flox/flox :PLP/CreER T mice, both oligodendrocyte differentiation and myelination proceed from the retinal to the chiasmatic end of the nerve (Thomson et al, 2005). First axonal contact of oligodendrocyte processes can be seen at the retinal end around postnatal day (P) 6.…”

Adenosine Kinase Expression Modulates Expression of Myelin Proteolipid Protein

“…Mechanistically, this could be due either to a failure in shutting off the synthesis of PLP or a failure to shut off oligodendrocyte precursor cell activation. Most remarkably, under conditions of high ADK, the expression of the alternatively spliced PLP-isoform DM20 -a marker of immature myelin [22] -is not turned off. Irrespective of the underlying mechanism, our findings suggest that in adult brain, adenosine can modulate the expression of an important myelin protein with putative neuroprotective functions.…”

“…In line with elevated hindbrain ADK our Western Blot analysis showed a 36 % increase in PLP expression in the hindbrain of both Adktg and fb-Adk-def mice compared to wild-type controls (n = 3 each). Interestingly, overexpression of PLP was accompanied by increased expression of DM20 an alternative splice product of PLP, which normally is expressed at higher levels during earlier developmental timepoints [22]. At this developmental time point myelination in hindbrain is more advanced than in forebrain, since myelination proceeds in a caudo-rostral direction.…”