Regulation and developmental expression of periaxin in the peripheral nervous system

• Main Author: Sherman, Diane Lynn
• Published: University of Edinburgh 1998
• Subjects: 573.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.661853

The localization of L- and S-periaxin was studied in the developing axon-Schwann cell unit where both proteins were localized to myelin-forming cells. During initial axonal ensheathment L-periazin was detected at the Schwann cell plasma membrane and in uncompacted myelin whorls. In early postnatal nerve it was concentrated in the adaxonal (apposing the axon) and abaxonal (apposing the basal lamina) membranes, but as the myelin sheath matures, L-periaxin became predominantly localized to the abaxonal Schwann cell membrane demonstrating a dynamic change in localization during development and ensheathment. This shift in localization of the protein after completion of the spiralization phase of myelination suggests that it participates in stabilizing the mature myelin sheath. In contrast, S-periaxin was not associated with membranes but appeared to be present throughout the Schwann cell cytoplasm. Both proteins were excluded from compact myelin. During embryogenesis Schwann cell precursor cells develop from migrating neural crest cells. At around E14.5 in the mouse sciatic nerve the precursor cells differentiate to form embryonic Schwann cells which in turn become either myelin-forming or non-myelin-forming Schwann cells in the mature PNS. In contrast to the mRNA for the major myelin protein P0, which is expressed in neural crest cells, L-periaxin mRNA and protein were first detected in embryonic Schwann cells. S-periaxin was detectable somewhat later at post-natal day 1. L-periaxin protein was not expressed in the non-myelin-forming Schwann cells of the sympathetic trunk and is therefore the earliest known marker for myelin-forming Schwann cells, also indicating that as early as E14.5 Schwann cells are committed to either a myelin-forming or non-myelin-forming lineage. L-periaxin was initially detected in the nuclei of embryonic Schwann cells; however it was predominantly localized to the plasma membrane by E17.5. The regulation of the <I>periaxin</I> gene was investigated by transgenesis. It was shown that a region of 5.5 kb upstream from the transcription initiation site could direct expression to a subset of myelinating Schwann cells as well as cells in the central nervous system indicating the presence of a neuronal silencer in the <I>periaxin </I>gene.