The Development of Germline Stem Cells in Drosophila

Abstract

SummaryGermline stem cells (GSCs) in Drosophila are a valuable model to explore of how adult stem cells are regulated in vivo. Genetic dissection of this system has shown that stem cell fate is determined and maintained by the stem cell's somatic microenvironment or niche. In Drosophila gonads, the stem cell niche-the cap cell cluster in females and the hub in males-acts as a signaling center to recruit GSCs from among a small population of undifferentiated primordial germ cells (PGCs). Shortrange signals from the niche specify and regulate stem cell fate by maintaining the undifferentiated state of the PGCs next to the niche. Germline cells that do not receive the niche signals because of their location assume the default fate and differentiate. Once GSCs are specified, adherens junctions maintain close association between the stem cells and their niche and help to orient stem cell division so that one daughter is displaced from the niche and differentiates. In females, stem cell fate depends on bone morphogenetic protein (BMP) signals from the cap cells; in males, hub cells express the cytokine-like ligand Unpaired, which activates the Janus kinase-signal transducers and activators of transcription (Jak-Stat) pathway in stem cells. Although the signaling pathways operating between the niche and stem cells are different, there are common general features in both males and females, including the arrangement of cell types, many of the genes used, and the logic of the system that maintains stem cell fate. KeywordsDrosophila; germline stem cell; GSC; PGC; primordial germ cell; stem cell fate; stem cell niche IntroductionStem cells are defined by their capacity to self-renew and to generate daughters that differentiate into one or more terminal cell types. Proper regulation of this property is critical for animal development, growth control, and reproduction. Understanding stem cell function is potentially very important for future developments in gene therapies and regenerative medicine. Research in Drosophila on germline stem cells (GSCs) has been instrumental in defining the important function of the stem cell's somatic microenvironment or niche in the control of its division and self-renewal (1,2). The Drosophila germline is an excellent model of stem cell biology because the system is genetically tractable, the sterility and rudimentary gonads resulting from GSC loss are easily recognized, and the stem cells can be easily identified based on molecular markers and position in the gonad. Germline morphology and development, from embryogenesis to the differentiation of gametes in adult flies, has been well characterized and offers a solid basis for the study of GSC fate determination, maintenance, and differentiation.Drosophila GSCs are derived from embryonic pole cells, the first cell type defined in the embryo. They migrate from the posterior to meet the somatic gonadal precursors (SGPs) and form the embryonic gonad, a simple structure made up of about ten primordial germ cells (PGCs) intermingled with and surr...

Separation of stem cell maintenance and transposon silencing functions of Piwi protein

“…This process is known to depend on Piwi expression only in somatic cells forming the GSC niche at the anterior-most end of the germarium (2, 6). The GSC niche consists of the terminal filament, escort cells, and cap cells, which directly associate with GSCs via adherens junctions (11,30). In the WT germarium, Piwi is known to be strongly stained in the nuclei of niche cells and GSCs, weakly stained in cystoblasts and early mitotic cysts, and strongly stained in late mitotic and differentiating 16-cell cysts (3,6).…”

“…Although several suppressors of piwi mutations restoring GSC maintenance were identified (7)(8)(9)(10), the key niche signal regulated by piwi remains unknown (reviewed in refs. 11,12). It was also shown that the intrinsic expression of Piwi in GSCs promotes their mitotic divisions (3,6).…”

Arginine methylation of Aubergine mediates Tudor binding and germ plasm localization

“…Specification of primordial germ cells (PGCs) in the developing Drosophila embryo requires maternal inheritance of cytoplasmic factors that are concentrated in the posterior pole in an area known as the pole or germ plasm (Ephrussi and Lehmann 1992;Jongens et al 1992;Williamson and Lehmann 1996;Houston and King 2000;Mahowald 2001;Strome and Lehmann 2007;Bastock and St Johnston 2008;Dansereau and Lasko 2008). Pole plasm contains electron-dense granules and related amorphous material that is rich in ribonucleoproteins and mitochondria; it is related to nuage, which surrounds the nurse cell nuclei and contains some of the same components (Dansereau and Lasko 2008;Chuma et al 2009).…”

“…Pole plasm contains electron-dense granules and related amorphous material that is rich in ribonucleoproteins and mitochondria; it is related to nuage, which surrounds the nurse cell nuclei and contains some of the same components (Dansereau and Lasko 2008;Chuma et al 2009). Similar electron-dense amorphous material often in close apposition to mitochondria is found in the cytoplasm of germ cells in various species and is known as P granules in C. elegans, germinal granules in Xenopus, and intermitochondrial cement and chromatoid bodies in mice (Dansereau and Lasko 2008;Chuma et al 2009).…”

“…Pole plasm contains electron-dense granules and related amorphous material that is rich in ribonucleoproteins and mitochondria; it is related to nuage, which surrounds the nurse cell nuclei and contains some of the same components (Dansereau and Lasko 2008;Chuma et al 2009). Similar electron-dense amorphous material often in close apposition to mitochondria is found in the cytoplasm of germ cells in various species and is known as P granules in C. elegans, germinal granules in Xenopus, and intermitochondrial cement and chromatoid bodies in mice (Dansereau and Lasko 2008;Chuma et al 2009). A set of maternally expressed genes (often referred to as posterior group or grandchildless genes) are required for PGC specification (Schupbach and Wieschaus 1986), and invariably the protein or RNA products of these genes are concentrated in the pole plasm and are incorporated in PGCs (Ephrussi and Lehmann 1992;Williamson and Lehmann 1996;Houston and King 2000;Mahowald 2001;Strome and Lehmann 2007;Bastock and St Johnston 2008;Dansereau and Lasko 2008).…”