Sexually reproducing metazoans establish a cell lineage during development that is ultimately dedicated to gamete production. Work in a variety of animals suggests that a group of conserved molecular determinants function in this germ line maintenance and function. The most universal of these genes are vasa and vasa-like DEAD box RNA helicase genes. However, recent evidence indicates that vasa genes also function in other cell types, distinct from the germ line. Here we evaluate our current understanding of vasa function and its regulation during development, addressing vasa’s emerging role in multipotent cells. We also explore the evolutionary diversification of the amino-terminal domain of this gene and how this impacts the association of vasa with nuage-like perinuclear structures.

Vasa is a DEAD-box RNA helicase that functions in translational regulation of specific mRNAs. In many animals it is essential for germ line development and may have a more general stem cell role. Here we identify vasa in two sea urchin species and analyze the regulation of its expression. We find that vasa protein accumulates in only a subset of cells containing vasa mRNA. In contrast to vasa mRNA, which is present uniformly throughout all cells of the early embryo, vasa protein accumulates selectively in the 16-cell stage micromeres, and then is restricted to the small micromeres through gastrulation to larval development. Manipulating early embryonic fate specification by blastomere separations, exposure to lithium, and dominant-negative cadherin each suggest that, although vasa protein accumulation in the small micromeres is fixed, accumulation in other cells of the embryo is inducible. Indeed, we find that embryos in which micromeres are removed respond by significant up-regulation of vasa protein translation, followed by spatial restriction of the protein late in gastrulation. Overall, these results support the contention that sea urchins do not have obligate primordial germ cells determined in early development, that vasa may function in an early stem cell population of the embryo, and that vasa expression in this embryo is restricted early by translational regulation to the small micromere lineage.

We used gene expression profiling to probe differences in transcriptional output between 15 panels of colon tumor and matched normal colon tissues. This analysis revealed that GPR49, an orphan G Protein-Coupled Receptor (GPCR) is overexpressed in 66% (10/15) colon tumors compared with normal colon tissues. Subsequent analysis of an additional 39 sets of matched normal and tumor colon tissues by real-time quantitative reverse transcriptase confirmed the upregulation of this receptor. The differential expression of GPR49 between normal and tumor tissue was significant (p > 0.001). GPR49 was upregulated in 25 of 39 (64%) colon primary tumor tissues. In addition to colon tumors, GPR49 was also found to be upregulated in 18 of 33 (53%) ovarian primary tumor tissues analyzed by RT-PCR. Moreover, the expression level of GPR49 in colon and ovarian tumors increased in more advanced tumors suggesting a role for the receptor in tumor progression. The selective overexpression of GPR49 in tumor tissues was further illustrated by specific immunohistochemical staining of colon and ovarian tumor tissues, a finding that correlates with the mRNA expression of the receptor. In addition, expression of GPR49 induced transformation in a ligand-dependent manner and Knockdown of GPR49 mRNA level induced apoptosis in colon tumor cells. These novel findings provide a foundation for further studies and suggest a potential role for GPR49 in tumorigenesis.