Destabilisation of bam transcripts terminates the mitotic phase of Drosophila female germline differentiation

The tight control of the mitotic phase of differentiation is crucial to prevent tumourigenesis while securing tissue homeostasis. In the Drosophila female germline, differentiation involves precisely four mitotic divisions, and accumulating evidence suggests that bag of marbles (bam), the initiator of differentiation, is also involved in controlling the number of divisions. To test this hypothesis, we depleted Bam from differentiating cells and found a reduced number of mitotic divisions. We examined the regulation of Bam using RNA imaging methods and found that the bam 3' UTR conveys instability to the transcript in the eight-cell cyst and early 16-cell cyst. We show that the RNA-binding protein Rbp9 is responsible for timing bam mRNA decay. Rbp9 itself is part of a sequential cascade of RNA-binding proteins activated downstream of Bam, and we show that it is regulated through a change in transcription start site, driven by Rbfox1. Altogether, we propose a model in which Bam expression at the beginning of differentiation initiates a series of events that eventually terminates the Bam expression domain.