Patterning of phase-separated condensates by Dnd1 controls cell fate

Abstract

Germ granules, condensates of phase-separated RNA and protein, are essential for germline development, but how these molecules are organized within the granules and whether such an organization is relevant for germ cell fate is unclear. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the vertebrate-specific Dead end protein is essential for positioningnanos3RNA at the periphery of the condensates, where ribosomes are located. Without Dead end, or when translation is inhibited,nanos3RNA translocates into granule interiors, far from the location of the ribosomes. These findings reveal the molecular mechanisms controlling the spatial organization of RNA within the phase-separated organelle and the importance of sub-granule RNA localization for preserving germ cell totipotency.

P-body-like condensates in the germline

“…The Drosophila CCR4 deadenylase colocalizes with Nanos in some foci in female germline stem cells [ 51 ], but Nanos localization with P-body components in other tissues has not been reported yet. Interestingly, loss of DND in zebrafish prevents efficient translation of Nanos on the surface of germ granules and causes germ cells to adopt somatic-like fates [ 121 , 41 ]. These phenotypes are reminiscent of those observed in C. elegans mutants that do not assemble germline P-bodies [ 18 ].…”