Modern tools applied to classic structures: Approaches for mammalian male germ cell RNA granule research

First reported in the 1800s, germ cell granules are small nonmembrane bound RNA-rich regions of the cytoplasm. These sites of critical RNA processing and storage in the male germ cell are essential for proper differentiation and development and are present in a wide range of species from Caenorhabditis elegans through mammals. Initially characterized by light and electron microscopy, more modern techniques such as immunofluorescence and genetic models have played a major role in expanding our understanding of the composition of these structures. While these methods have given light to potential granule functions, much work remains to be done. The current expansion of imaging technologies and omics-scale analyses to germ cell granule research will drive the field forward considerably. Many of these methods, both current and upcoming, have considerable caveats and limitations that necessitate a holistic approach to the study of germ granules. By combining and balancing different techniques, the field is poised to elucidate the nature of these critical structures.