In Drosophila melanogaster the progenitors of the adult germline, the primordial germ cells (PGCs), are formed at the posterior pole of the pre-cellular blastoderm embryo. The process of PGCs specification and development differs substantially from that of the surrounding soma. Amongst the differences are precocious cellularization, sequestration on the outside surface of the embryo, limited mitotic potential, transcriptional quiescence and a special chromatin architecture. Also unlike the soma, the specification and subsequent elaboration of PGC identity is thought to depend exclusively on cell autonomous factors that are assembled into a specialized cytoplasm, the pole plasm, at the posterior of the oocyte during oogenesis. In addition to orchestrating PGC development, these maternal factors are thought to insulate newly formed PGCs from the adverse effects of the cell-cell signaling pathways that are deployed to pattern the neighboring soma. However, our preliminary experiments on the BMP signaling pathway challenge this long held view of PGC specification. We find that PGCs are not only capable of responding to BMP signals from the soma, but also that these signals impact the specification and development of the PGCs. In the studies outlined in this application we propose to re-examine the problem of PGC specification, focusing on the role of this non-autonomous signaling pathway in PGC development. We will investigate several issues that are central to our understanding of the mechanisms underlying how PGC fate is determined and how the PGCs subsequently development into germline stem cells (GSCs). We will determine what role the BMP signaling pathway plays in the developing PGCs in the period between the formation of these cells in the early embryo and their coalescence into the embryonic gonad during mid-embryogenesis. In mid-embryogenesis, our studies will focus on how this pathway impacts the transformation of PGCs into GCSs. We will also analyze an unexpected and novel role of the BMP pathway in the feminization of the PGCs/GSCs. In the early embryo, our studies will focus on the mechanisms involved in the specification and maintenance of PGC identity. We will investigate how the BMP pathway intersects with the cell autonomous maternal factors to establish and elaborate PGC fate. We will also determine whether the BMP pathway plays an instrumental role in programming PGC specific patterns of gene activity.
In Drosophila, primordial germ cells (PGCs) eventually give rise to the Germline Stem Cells (GSCs). It is thus crucial to decipher the mechanisms underlying the determination of germ cell identity, as GSCs are the totipotent precursors of all the cell types in an organism. We have uncovered a non-autonomous signaling influence involving BMP pathway that contributes to the specification of PGCs.
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