Smad-Independent BMP Signaling in Somatic Cells Limits the Size of the Germline Stem Cell Pool

Abstract

SummaryIn developing organisms, proper tuning of the number of stem cells within a niche is critical for the maintenance of adult tissues; however, the involved mechanisms remain largely unclear. Here, we demonstrate that Thickveins (Tkv), a type I bone morphogenetic protein (BMP) receptor, acts in the Drosophila developing ovarian soma through a Smad-independent pathway to shape the distribution of BMP signal within the niche, impacting germline stem cell (GSC) recruitment and maintenance. Somatic Tkv promotes Egfr signaling to silence transcription of Dally, which localizes BMP signals on the cell surface. In parallel, Tkv promotes Hh signaling, which promotes escort cell cellular protrusions and upregulates expression of the Drosophila BMP homolog, Dpp, forming a positive feedback loop that enhances Tkv signaling and strengthens the niche boundary. Our results reveal a role for non-canonical BMP signaling in the soma during GSC establishment and generally illustrate how complex, cell-specific BMP signaling mediates niche-stem cell interactions.

The exocyst functions in niche cells to promote germline stem cell differentiation by directly controlling EGFR membrane trafficking

“…Accumulated experimental evidence demonstrates that ISCs function as a niche to prevent BMP signaling and promote GSC progeny differentiation via multiple signaling pathways (Eliazer et al, 2014(Eliazer et al, , 2011Kirilly et al, 2011;Li et al, 2015;Liu et al, 2010Liu et al, , 2015Lu et al, 2015;Luo et al, 2015;Ma et al, 2014;Maimon et al, 2014;Su et al, 2018;Tseng et al, 2018;Wang et al, 2015Wang et al, , 2011Wang and Page-McCaw, 2018). In addition, long ISC cellular process-mediated interactions are crucial for proper GSC progeny differentiation partly by repressing BMP signaling and also potentially through direct signaling (Banisch et al, 2017;Kirilly et al, 2011;Lu et al, 2015;Maimon et al, 2014;Su et al, 2018;Tseng et al, 2018). However, it remains largely unclear how ISC long cellular processes and ISC-operating signaling pathways are regulated at the cellular level.…”

“…In addition, Rho prevents BMP signaling by repressing dally and dpp in ISCs, whereas Eggless, Piwi, Lsd1, Hh signaling and the COP9 complex repress dpp in ISCs (Eliazer et al, 2014(Eliazer et al, , 2011Huang et al, 2017;Jin et al, 2013;Kirilly et al, 2011;Liu et al, 2015;Lu et al, 2015;Ma et al, 2014;Wang et al, 2015Wang et al, , 2011. Tkv acts in ISCs to prevent Dpp diffusion and promote Hh signaling, thereby preventing BMP signaling (Luo et al, 2015;Tseng et al, 2018). Thus, ISCs promote GSC progeny differentiation primarily by preventing BMP signaling.…”

Modulation of Cell–Cell Interactions in Drosophila Oocyte Development

“…Thus, the establishment and maintenance of a sharp Dpp gradient across the anterior part of the germarium is critical to limit the niche space. Multiple mechanisms have been reported to restrict and ensure Dpp signal range within one cell diameter wide so that it only activates GSCs but not cystoblasts [6,[23][24][25][26][27][28][29][30][31][32][33][34].…”

Mad dephosphorylation at the nuclear envelope is essential for asymmetric stem cell division

“…The downregulation of bam is essential for GSC self-renewal (Xie and Spradling, 1998) , (Song, 2004;Akbar et al, 2009;, Chen and McKearin, 2003a). Multiple studies have defined mechanisms for fine-tuning Dpp signal strength and range (Xia et al, 2012;Wang et al, 2008;Van De Bor et al, 2015;Wilcockson and Ashe, 2019;Guo and Wang, 2009;Harris et al, 2011;Liu et al, 2010;Schulz et al, 2002;Xia et al, 2010;Jiang et al, 2008;Tseng et al, 2018).…”