DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

•DAZL colocalizes with a network of translational inhibitors in granular structures•DAZL interacts with mRNA transcripts of key pluripotency genes and Caspases•Loss of DAZL function leads to prolonged expression of pluripotency genes•Loss of DAZL leads to expression of Caspases, resulting in apoptosis in PGCs

SummaryThe scarcity of primordial germ cells (PGCs) in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide