Cis-inhibition of Notch by Delta controls follicle formation in Drosophila melanogaster

Abstract

Daughters of stem cells often differentiate sequentially in response to inputs from various signalling molecules. We focus on the regulation of Notch signalling in the Drosophila germarium. This structure contains several somatic stem cells, which give rise to polar cell or follicular cells precursors. Notch, which is required to form follicles, has been shown to be activated in some stem cells and in the polar cell precursors by a Delta signal produced by the germline cells. However, it is known that removing Delta from the germline does not phenocopy Notch phenotype, indicating that the mechanism of N activation and its role remain unclear. Here, we demonstrate that Delta in the soma buffers Notch activity via a cis-inhibition mechanism, resulting in the maintenance of an undifferentiated state. In the somatic stem cells and in the polar cell precursors, somatic Delta prevents Notch from being activated by Delta from the germline or from the soma, respectively. Our data also show that these two steps of Notch activities play a redundant role in follicle formation. Thus, Notch activity depends on both germline and somatic Delta, explaining the phenotype discrepancies between Notch and Delta ovaries. In addition, we show that somatic Delta is more efficient in initiating pc differentiation than germline Delta. Finally, our work provides a novel example of the importance of the regulation of Notch activity through a cis-inhibitory mechanism.