Distinct mechanisms of germ cell factor regulation for an inductive germ cell fate

Abstract

Specification of primordial germ cells (PGCs), the lineage which gives rise to eggs and sperm, is essential for sexually reproducing organisms. The mechanism by which animals specify their PGCs generally falls into two categories: inherited or inductive. The inductive mechanism, used by mammals, relies on cell signaling interactions to direct a subset of embryonic cells to a germ cell fate. Previous work suggested that sea star embryos, which develop in simple culture and are markedly transparent, also use inductive mechanisms to specify their germline. The germ cell factors Nanos and Vasa become restricted during early development into a localized region of cells within the posterior enterocoel (PE), the presumptive germline. Nodal signaling was observed to negatively regulate Vasa and Nanos mRNAs outside of the PE and restrict the germline to the PE. Here we employed single cell RNA sequencing to identify the transcriptional program of germ cells and their changes during development. We never see Nodal pathway members within Nanos/Vasa positive cells in the region known to give rise to the PE, and instead see members of the Wnt-signaling pathway and the FoxY family of transcription factors. We learned that Wnt and Delta/Notch signaling enhances expression of both Nanos and Vasa, whereas a test of cell interactions reveals that Nanos and Vasa are regulated distinctly. This work provides insights into the sequence of events that leads to PGC specification and enables deeper mechanistic studies in a tractable in vivo model. HighlightsO_LISingle-cell RNA-sequencing of sea star embryos demonstrates temporal differences in cell fate commitment among echinoderms. C_LIO_LISea urchin and sea star embryos appear to ascribe their germ line by two extreme different mechanisms but share similar pathways in regulation of the germline genes. C_LIO_LIExpression of the germline factors, Vasa and Nanos, is regulated by distinct mechanisms in the sea star. C_LIO_LIGermline induction in the sea star uses similar signaling mechanisms as mammals. C_LI