C. elegans sperm initially accumulate as spherical non-motile spermatids, and mature to amoeboid crawling spermatozoa upon exposure to an external activator. This maturation process, termed spermiogenesis, depends on a signaling pathway mediated by at least four genes--
spe-8,
spe-12,
spe-27, and
spe-29. Mutations in any of these genes severely disrupt transduction of the hermaphrodite-supplied activation signal, but only moderately interfere with signaling from the male-supplied activator. This leads to a peculiar phenotype: unmated hermaphrodites are self-sterile, but hermaphrodites mated to mutant males are both cross- and self-fertile. Mutations in any of these genes are suppressed by certain alleles of
spe-6, which we identified as a member of a large family of casein kinase I genes in C. elegans. We have proposed that the SPE-6 kinase acts as an inhibitor of spermiogenesis, and that, upon exposure to the activation signal, SPE-8, SPE-12, SPE-27, and SPE-28 act to relieve inhibition by SPE-6. To understand how these genes signal sperm maturation, we have sought to identify them and characterize their products.
spe-8 had been the only gene in the group remaining to be cloned. By combining classical genetics studies of
spe-8 mutants with microarray studies cataloging the spermatogenesis-specific genes in the worm, we have now identified SPE-8 (encoded by F53G12.6) as an SH2-domain-containing non-receptor tyrosine kinase, most closely related to the Fes/Fps avian sarcoma oncogenes. Like
spe-6,
spe-8 belongs to a large gene family, containing 39 paralogs, most of which appear to be spermatogenesis-specific or enriched. We are currently attempting to understand the subcellular localization of SPE-8, and to identify its substrate(s).