Vasa, nanos and germline multipotency program genes

Wilson (1896) described Weismann's germ-plasm as chromatin with a complex fixed architecture. It was transmitted between generations and fixed the course of embryonic development in a definite way.¹ Rádl (1930) set out the consequence: the germ-plasm, shut up in the reproductive cells, cannot be influenced by bodily changes such as injury, exercise or habitat.² Child (1924) objected that current heredity theories gave no mechanism for development and differentiation. In his account, each cell was held to carry the whole chromosomal mechanism, with no sorting out during development.³ Early writers such as Wilson, Rádl and Child treated germ plasm as a hereditary substance, without naming specific molecules.

Solana (2013) wrote that germ plasm contains several proteins and mRNAs, including Vasa, Nanos and Piwi, typically in electron-dense granules.⁴ The granules have different names in different species. Collectively they are called nuage, and they occur in egg cells and zygotes of many species as well as in germ cells.⁴ Solana added that the classical term germ plasm is hard to translate into a molecular definition. The closest approximation is the program as underlying circuitry, which may be a collection of circuits and not one indivisible block.⁵ Granule shape, size and number vary between organisms. Tiny vasa- and nanos-positive granules in early cephalochordate cleavage suggest germline specification by preformation.⁵

Solana reported that several germ plasm components are expressed in tissues classically considered somatic. The examples were planarian neoblasts, the posterior growth zone of polychaetes, hydrozoan interstitial stem cells and the small micromere lineage of echinoderm embryos.⁴ These findings led to the proposal of a conserved germline multipotency program.⁴ Rink (2013) listed neoblast-like cells in annelids and acoels. Rink also noted that ctenophores and cnidarians keep stem cell systems expressing piwi, vasa and nanos, and that sponges have piwi-positive stem cells that give rise to the germ line.⁶ Lobo, Beane and Levin (2012) reported that blocking innexin-11 removes piwi-positive cells and the ability to regenerate.⁹

Rink described work on the methyltransferase Smed-PRMT-5. It methylates RNA-binding proteins including PIWI and Vasa, creating docking sites for TUDOR-domain proteins. This gives a scaffold for ribonucleoprotein complexes such as germ granules.⁷ Rouhana and colleagues found that PRMT-5 RNAi gradually depleted neoblasts and killed the animals. Transposon transcription rose at the same time.⁷ They added that the role in somatic tissues is less clear.⁸