User:Elemp46/sandbox

There are two mechanisms to establish the germ cell lineage in the embryo. The first way is called preformistic and involves that the cells destined to become germ cells inherit the specific germ cell determinants present in the germ plasm (specific area of the cytoplasm) of the egg (ovum). The unfertilized egg of most animals is asymmetrical: different regions of the cytoplasm contain different amounts of mRNA and proteins.

The second way is found in birds and mammals, where germ cells are not specified by such determinants but by signals controlled by zygotic genes. In mammals, a few cells of the early embryo are induced by signals of neighboring cells to become primordial germ cells. Mammalian eggs are somewhat symmetrical and after the first divisions of the fertilized egg, the produced cells are all totipotent. This means that they can differentiate in any cell type in the body and thus germ cells. Specification of primordial germ cells in the laboratory mouse is initiated by high levels of bone morphogenetic protein (BMP) signaling, which activates expression of the transcription factors Blimp-1/Prdm1 and Prdm14

It is speculated that induction was the ancestral mechanism, and that the preformistic, or inheritance, mechanism of germ cell establishment arose from convergent evolution. There are several key differences between these two mechanisms that may provide reasoning for the evolution of germ plasm inheritance. One difference is that typically inheritance occurs almost immediately during development (around the blastoderm stage) while induction typically does not occur until gastrulation. As germ cells are quiescent and therefore not dividing, they are not susceptible to mutation. Since the germ cell lineage is not established right away by induction, there is a higher chance for mutation to occur before the cells are specified. Mutation rate data is available that indicates a higher rate of germ line mutations in mice and humans, species which undergo induction, than in C. elegans and Drosophila melanogaster, species which undergo inheritance. A lower mutation rate would be selected for, which is one possible reason for the convergent evolution of the germ plasm. However, more mutation rate data will need to be collected across several taxa, particularly data collected both before and after the specification of primordial germ cells before this hypothesis on the evolution of germ plasm can be backed by strong evidence.

oskar is a gene required for the development of the Drosophila embryo. It defines the posterior pole during early embryogenesis. Its two isoformas, short and long, play different roles in Drosophila embryonic development.

Translational-level regulation[edit]

oskar is translationally repressed prior to reaching the posterior pole of the oocyte by Bruno, which binds to three bruno response elements (BREs) on the 3' end of the transcribed oskar mRNA. The Bruno inhibitor has two distinct modes of action: recruiting the Cup eIF4E binding protein, which is also required for oskar mRNA localization due to interactions with the Barentsz microtubule-linked transporter, and promoting oligomerization of oskar mRNA. Oskar mRNA harbours a stem-loop structure in the 3’UTR, called the oocyte entry signal (OES), that promotes dynein-based mRNA accumulation in the oocyte.

P Granule Formation

oskar plays role in recruiting other germ line genes to the germ plasm for PGC (primordial germ cell) specification. oskar mRNA locates to the posterior end of an oocyte and, once translated, the short isoform of oskar (Short oskar) recruits germ plasm components such as the protein Vasa and the RNA-binding proteins of the Piwi family, among many others. The long isoform of oskar (Long oskar) has been implicated in creating an actin network on the posterior pole end.

A second role has been discovered that relates to the formation of P granules, or germ granules. These ribonucleoprotein granules are found in every species' germ line cells. Although they are mobile, they typically localize to the nuclei and sit on nuclear pores. This positioning makes them ideal mRNA regulators, as the mRNA must pass through to exit the nucleus. Translational regulation also makes sense due to the granules' close association with ribosomes. These P granules are phase-transition entities, which means that they can display both liquid-like and hydrogel-like properties. This allows them to be very versatile structures, able to dissolve, condense, and exchange their protein content with their environment at will. Recent studies have shown that the short isoform of oskar has another function as the nucleator of nuclear germ granules. oskar recruits vasa to these round granules, then promotes the localization to the nucleus. oskar was ablated to explore the function of these nuclear germ granules. The results showed that the division of PGCs was compromised without oskar, meaning that the P granules play a role in the cell cycle of germ cells. It is still unclear exactly how the nuclear granules interact with certain factors and what factors (proteins, regulators, inhibitors) they interact with in order to regulate cell division.