Vasa genes: emerging roles in the germ line and in multipotent cells

Abstract

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 act 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 N-terminal domain of this gene and how this impacts the association of Vasa with nuage-like perinuclear structures.

Figure 1. Vasa gene family conservation

(A) Nine conserved sequence motifs specific to all DEAD-box genes. Residues important for ATP-binding and hydrolysis are indicated in green and residues involved in RNA binding are indicated in purple. The function of the remaining conserved motifs in white is unclear. (B) A schematic representation of the phylogenetic relationship between Vasa genes, PL10 genes and the closest related DEAD box gene, p68 (Adapted from Mochizuki et al., 2001). The star indicates the evolutionary split between Vasa and PL10 genes. (C) CCHC Zn-knuckle domain-containing Vasa genes from Table 1 were used to illustrate the phylogenetic conservation of this motif in the N-terminal portion of Vasa proteins. Animals with Vasa CCHC Zn-knuckles are indicated in red, animals lacking Vasa Zn-knuckles are shown in black and animals with insufficient Vasa sequence information are indicated in grey (Phylogenetic tree adapted from Dunn et al., 2008).

Figure 2. Vasa protein association with nuage-like structures

Vasa protein localizes to perinuclear structures in a wide variety of metazoans. C. elegans immunofluorescent imaging of Vasa protein (A) and TEM image of polar granules (B) (black arrows indicate nuclear pores). (C) In Drosophila melanogaster developing egg chamber, Vasa protein localizes to the pole plasm in the oocyte (white arrowhead) and the pernuclear nuage in nurse cells (red arrows). DIC (D) and Vasa immunoflourescence (E) imaging of a Ciona intestinalis gastrula embryo with both punctate (arrows) and diffuse (arrowheads). Vasa protein (F, immunofluorescence) localizes to the Balbiani body (G, TEM) in mouse oocytes. In mouse spermatids, chromatoid bodies (black arrows) (H, TEM) contain Vasa protein (white arrows) (I, immunoflourescence).