Structure and expression of a novel filarial gene for glia maturation factor

Factors that influence neural growth and development in parasitic nematodes have not yet been identified. We have isolated and sequenced a Brugia malayi nematode 3.4-kb genomic DNA fragment and its corresponding cDNA, which encode a predicted protein of 138 amino acids with 52% identity and 75% similarity to the mammalian neuroglial growth factor, glia maturation factor-beta (GMF). GMF promotes the differentiation of mammalian glia and neurons and stimulates axonal regeneration. The filarial nematode gene Bmgmf for Brugia malayi glia maturation factor contains six predicted exons, with the first exon encoding only the initiation methionine. Brugia malayi GMF (BmGMF) is also related to a large family of eukaryotic actin depolymerizing factors (ADFs). Although BmGMF does not contain the consensus actin-depolymerizing motif of ADFs, it does share a similar intron exon structure, including the unusual first exon, with the unc-60 ADF gene of the nematode Caenorhabditis elegans. RT-PCR experiments reveal that BmGMF is trans-spliced with the nematode spliced leader sequence SL1 and is expressed in microfilariae but not in third-stage larvae or adult worms. We speculate that BmGMF may function as a stage-specific neuroglial growth factor.