The deletion of a sperm-specific transcription factor causes cell cycle and sperm differentiation defects in Caenorhabditis elegans

Germ cells are highly dynamic in that they undergo several dramatic transitions throughout their lives. They begin as highly proliferative stem cells. Eventually, they become mitotically proliferating germ cell precursors. In Caenorhabditis elegans, these precursor cells do not even have a specified cell fate. Only after the cells move past the mitotic zone do the precursor cells enter meiosis and initiate the sexual specification process. As the gametes move through meiosis, sex-specific proteins are transcribed and translated. These proteins contribute to the differentiation pathway that creates a functional, haploid gamete. The regulation of these sperm-specific genes and proteins is not well understood. To further understand the process of how gametes progress through the early stages of meiosis, we examined a deletion mutation in the gene for a sperm-specific transcription factor, SPE-44. This deletion causes catastrophic failure of both the meiotic and differentiation pathways of spermatogenesis. spe-44 mutants fail to create functional sperm, as their cells arrest in M phase. Instead of sperm, spe-44 gonads contain terminal cells of varying size and composition. Smaller, older cells contain supernumerary microtubule asters and a variable amount of DNA. Phospho-histone H3, an M-phase marker, persists in the terminal, small cells of the mutant. As for sperm differentiation, spe-44 mutants contain the Major Sperm Protein (MSP) but fail to assemble it into paracrystals after synthesis. The membranous organelles (MOs), Golgi-derived and nematode sperm-specific organelles which associate with the assembled MSP paracrystals, mislocalize within the small cells of the mutant and fail to dock on the cell cortex. During wildtype spermatogenesis, the SPE-44 protein itself localizes to the chromatin of the developing spermatocytes during pachytene and disappears in the karyosome stage. Microarray data from Harold Smith of the NIH show that spe-44 mutants do not express many of the sperm-enriched genes that are necessary for sperm production in C. elegans. SPE-7, a nematode sperm-specific protein, is among the gene products not present in the spe-44 mutant. SPE-44 appears to function as the link between sperm specification and sperm production; it is the first sperm-specific transcriptional regulator in the C. elegans germ line to be described