Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c

Germ cell specification is driven, in many species, by germplasm: a collection of phase-separation-based structures in the embryo, formed by RNA and proteins that derive from the cytoplasm of the oocytes. How the formation of germplasm is regulated, especially in vertebrates, remains unclear. In this study, we show that two multi-Tudor proteins, Tdrd6a and Tdrd6c, together are necessary for the stability of germplasm in zebrafish, while the related Balbiani body in the oocyte is largely unaffected. Combined lack of maternal Tdrd6a and Tdrd6c still allows the initial germplasm formation but causes its dispersal during the first hours of development. This results in the absence of primordial germ cells during later development and in sterility of the resulting adult animals. Furthermore, our study suggests that the Prion-like domain of Tdrd6c is relevant for Tdrd6c self-interaction as well as for its interaction with Bucky ball, the organizer of germplasm in zebrafish and that these dynamics are modulated by Tdrd6c Tudor domains. The identification of Tdrd6a and Tdrd6c as required for germplasm stability is an important step in our understanding of how this phase-separated structure is controlled during development. Author SummaryWe show that maternal Tdrd6a and Tdrd6c proteins interact with Bucky Ball and are essential for embryonic germplasm stability, germ cell specification and fertility in zebrafish.