PRDM14 is essential for vertebrate gastrulation and safeguards avian germ cell identity

Abstract

The zinc finger transcription factor PRDM14, part of the PR domain containing protein family, is critical for mammalian primordial germ cell (PGC) specification, epigenetic reprogramming and maintaining naïve pluripotency in stem cells. However, PRDM14's role in other species is not well understood. In chicken, PRDM14 is broadly expressed in the early embryo, before becoming restricted to the forming neural plate, migratory PGCs, and later, in the adult testes. To investigate the role of PRDM14 we generated two independent targeted chicken lines and bred homozygous knockout embryos. Strikingly, we found that gastrulation was disrupted in PRDM14^−/− embryos, which lacked a definitive primitive streak. Transcriptomic and in situ hybridisation analyses revealed a broad loss of anterior primitive streak marker genes, coupled with downregulation of the multifunctional antagonists CHRD and CER1, and expansion of the NODAL expression domain. Further analysis of PRDM14^−/− embryos revealed PGCs were still specified but significantly reduced in number, and PRDM14^−/− PGCs could not be propagated in vitro. Knockdown studies in vitro confirmed that PRDM14 is essential for PGC survival and antagonises FGF-induced somatic differentiation, similar to PRDM14's role in mammalian stem cells. Taken together, our results show that in chicken, PRDM14 plays a multifunctional and essential role during embryonic development.