The Vertebrate Protein Dead End Maintains Primordial Germ Cell Fate by Inhibiting Somatic Differentiation

Gross-Thebing T., Yigit S., Pfeiffer J., Reichman-Fried M., Bandemer J., Ruckert C., Rathmer C., Goudarzi M., Stehling M., Tarbashevich K., Seggewiss J., Raz E.

Abstract

Maintaining cell fate relies on robust mechanisms that prevent the differentiation of specified cells into other cell types. This is especially critical during embryogenesis, when extensive cell proliferation, patterning, and migration events take place. Here we show that vertebrate primordial germ cells (PGCs) are protected from reprogramming into other cell types by the RNA-binding protein Dead end (Dnd). PGCs knocked down for Dnd lose their characteristic morphology and adopt various somatic cell fates. Concomitantly, they gain a gene expression profile reflecting differentiation into cells of different germ layers, in a process that we could direct by expression of specific cell-fate determinants. Importantly, we visualized these events within live zebrafish embryos, which provide temporal information regarding cell reprogramming. Our results shed light on the mechanisms controlling germ cell fate maintenance and are relevant for the formation of teratoma, a tumor class composed of cells from more than one germ layer. Primordial germ cells (PGCs) maintain their fate during their migration within the embryo. Through monitoring PGCs in live zebrafish embryos, Gross-Thebing et al. uncover a key role for the vertebrate-specific RNA-binding protein Dead end (Dnd) in protecting and maintaining germ cell fate. Dnd-deficient germ cells transdifferentiate into somatic cells.