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

Abstract

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 39 UTR conveys instability to the transcript in the 8-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 dawn of differentiation initiates a series of events that eventually terminates the Bam expression domain.