Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification

In recent years, it has become clear that membrane-less structures formed through phase separation represent an important class of subcellular compartmentalization. However, little is known about how the formation or disassembly of such compartments is regulated. The Balbiani body (Bb) is a phase-separated structure essential for germ cell specification and home to many germ cell-specific mRNAs and proteins. Throughout oogenesis, the structure assembles all critical components required for germ cell induction upon fertilization, then referred to as germ plasm (Gp). In zebrafish, formation of the Bb requires Bucky ball (Buc), a protein with prion-like properties. We have found that Tdrd6a interacts directly with Buc and regulates its aggregation into a functional Bb. Without Tdrd6a, the morphology and mobility of the Bb and the Gp are severely affected, ultimately resulting in PGC depletion in the progeny. Since germ cells are rich in phase-separated structures, many more of such regulatory interactions exist.