Abstract: Stemcells interact with surrounding stromal cells (or niche) via signaling pathways to precisely balance stemcell self-renewal and differentiation. However, little is known about how niche signals are transduced dynamically and differentially to stemcells and their intermediate progeny and how the fate switch of stemcell to differentiating cell is initiated. The Drosophila ovarian germlinestemcells (GSCs) have provided a heuristic model for studying the stemcell and niche interaction. Previous studies demonstrated that the niche-dependentBMP signaling is essential for GSC self-renewal via silencing bam transcription in GSCs. We recently revealed that the Fused (Fu)/Smurf complex degrades the BMP type I receptor Tkv allowing for bam expression in differentiating cystoblasts (CBs). However, how the Fu is differentially regulated in GSCs and CBs remains unclear. Here we report that aniche-dependentfeedbackloop involving Tkv and Fu produces a steep gradient of BMPactivity and determines GSC fate. Importantly, we show that Fu and graded BMPactivity dynamically develop within an intermediate cell, the precursor of CBs, during GSC-to-CB transition. Our mathematic modeling reveals a bistable behavior of the feedback-loop system in controlling the bam transcriptional on/off switch and determining GSC fate.

 

Laixin Xia, Xiudeng Zheng, Wenjing Zheng, Guoqiang Zhang, Hailong Wang, Yi Tao, Dahua Chen. 2012. The niche-dependent feedback loop generates a BMP activity gradient to determine the germline stem cell fate. Current Biology. 22(6): 515-521.(URL)