Abstract

SummaryIn the Drosophila ovarian germline, Bone Morphogenetic Protein (BMP) signals released by niche cells promote germline stem cell (GSC) maintenance. Although BMP signaling is known to repress expression of a key differentiation factor, it remains unclear whether BMP-responsive transcription also contributes positively to GSC identity. Here, we identify the GSC transcriptome using RNA sequencing (RNA-seq), including the BMP-induced transcriptional network. Based on these data, we provide evidence that GSCs form two types of cellular projections. Genetic manipulation and live ex vivo imaging reveal that both classes of projection allow GSCs to access a reservoir of Dpp held away from the GSC-niche interface. Moreover, microtubule-rich projections, termed “cytocensors”, form downstream of BMP and have additional functionality, which is to attenuate BMP signaling. In this way, cytocensors allow dynamic modulation of signal transduction to facilitate differentiation following GSC division. This ability of cytocensors to attenuate the signaling response expands the repertoire of functions associated with signaling projections.

Highlights

  • The stem cell niche is a tissue microenvironment, specialized in structure and function, that ensures the self-renewal and survival of cells needed to maintain tissue homeostasis throughout an organism’s life

  • Multiple mechanisms have been described for restricting Dpp range, including stabilization or concentration of Dpp within the niche by the heparan sulphate proteoglycan (HSPG) Divisions abnormally delayed (Dally), sequestration by a collagen IV (CollIV) matrix between the germline stem cell (GSC) and cap cells (CpCs), and escort cell (EC) expression of the Dpp receptor, Thickveins (Tkv), which acts as a ‘‘decoy’’ to soak up any free Bone Morphogenetic Protein (BMP) ligand (Wilcockson et al, 2017)

  • RNA-Seq of GSC-like Cells and CBs Reveals Putative GSC Self-Renewal and Maintenance Factors In order to identify regulators of GSC self-renewal and differentiation, we compared the GSC and CB transcriptomes by purifying these cells based on the expression of known cellular markers

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Summary

Introduction

The stem cell niche is a tissue microenvironment, specialized in structure and function, that ensures the self-renewal and survival of cells needed to maintain tissue homeostasis throughout an organism’s life. The first niche was characterized in the Drosophila ovarian germline (Cox et al, 1998; King and Lin, 1999) where the Bone Morphogenetic Protein (BMP) family member, Decapentaplegic (Dpp), was found to be necessary for maintenance of germline stem cells (GSCs) (Xie and Spradling, 1998, 2000). Since this discovery, there has been an explosion in the identification and characterization of stem cell niches in most tissues and model organisms (Scadden, 2014). The most anterior ECs define the posterior limit of the GSC niche and contact the differentiating CBs to create a differentiation niche

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