Germline stem cells in the Drosophila ovary descend from pole cells in the anterior region of the embryonic gonad

A fundamental yet unexplored question in stem cell biology is how the fate of tissue stem cells is initially determined during development. In Drosophila, germline stem cells (GSCs) descend from a subset of primordial germ cells (PGCs) at the onset of oogenesis. GSC determination may occur at the onset of oogenesis when a subset of PGCs is induced to become GSCs by contacting niche cells. Alternatively, the GSC fate could be predetermined for a subset of PGCs before oogenesis, due to either their interaction with specific somatic cells in the embryonic/larval gonads, or their inherently heterogeneous potential in becoming GSCs, or both. Here, we show that anterior somatic cells in the embryonic gonad already differ from posterior somatic cells and are likely to be the precursors of niche cells in the adult ovary. Furthermore, only pole cells in the anterior half of the embryonic gonad give rise to the PGCs that frequently acquire contact with nascent niche cells in the late larval ovary. Eventually, only these contacting PGCs become GSCs, whereas non-contacting PGCs directly differentiate into cystoblasts. The strong preference of these 'anterior PGCs' towards contacting niche cells does not require DE-cadherin-mediated adhesion and is not correlated with either orientation or rate of their divisions. These data suggest that the GSC fate is predetermined before oogenesis. The predetermination probably involves soma/pole-cell interaction in the anterior half of the embryonic gonad, followed by an active homing mechanism during PGC proliferation to maintain the contact between the 'anterior PGCs' and anterior somatic cells.