Different Mechanisms Regulate Expression of Zebrafish Myelin P0 in Myelinating Oligodendrocytes and its Induction Following Axonal Injury [Molecular Bases of Disease]
July 15th, 2014 by Bai, Q., Parris, R. S., Burton, E. A.
Zebrafish CNS axons regenerate robustly following injury; it is thought that CNS oligodendrocytes contribute to this response by expressing growth-promoting molecules. We characterized the mpz gene, which encodes myelin P0 and is upregulated in oligodendroglia following axonal injury. The 2.5kb mpz mRNA is expressed from a single TATA-box promoter. Four independent Tg(mpz:egfp) transgenic zebrafish lines, in which GFP was expressed under the mpz promoter and 10kb of genomic 5' flanking sequence, showed transgene expression in CNS oligodendrocytes from larval development through adulthood. Following optic nerve crush injury, the mpz:egfp transgene was strongly upregulated in oligodendrocytes along the regenerating retinotectal projection, mirroring upregulation of endogenous mpz mRNA. GFP-expressing oligodendroglia were significantly more abundant in the regenerating optic pathway, resulting from both transgene induction in oligodendroglial precursors and birth of new cells. Upregulation of mpz was not dependent on axonal regeneration, suggesting that the primary signal may be axonal loss, debris or microglial infiltration. Deletion experiments indicated that an oligodendroglial enhancer located in the region -6kb to -10kb with respect to the mpz transcriptional start site is dissociable from the cis-regulatory element mediating the mpz transcriptional response to axonal injury, which is located between -1kb and -4kb. These data show that different mechanisms regulate expression of zebrafish mpz in myelinating oligodendrocytes and its induction following axonal injury. The underlying molecular events could potentially be exploited to enhance axonal repair following mammalian CNS injury. The transgenic lines and cis-regulatory constructs reported here will facilitate identification of the relevant signaling pathways.