Abstract
Specialized microenvironments called niches help maintain stem cells in an undifferentiated and self-renewing state. The existence of niches has long been predicted from mammalian studies, but identifying stem cells in their native environments in vivo has remained a challenge in most vertebrates. Many of the mechanistic insights into how niches regulate stem cell maintenance have been obtained using invertebrate models such as Drosophila. Here, we focus on the Drosophila ovarian germline stem cell niche and review recent studies that have begun to reveal how intricate crosstalk between various signaling pathways regulates stem cell maintenance, how the extracellular matrix modulates the signaling output of the niche and how epigenetic programming influences cell development and function both inside and outside the niche to ensure proper tissue homeostasis. These insights will probably inform the study of mammalian niches and how their malfunction contributes to human disease.
Highlights
Stem cells are essential for tissue homeostasis, in organs that exhibit high rates of cellular turnover such as the skin, intestine and hematopoietic system
Twenty years following Schofield’s seminal publication, Xie and Spradling provided compelling experimental evidence that a cellular niche supports the maintenance of germline stem cells (GSCs) in the Drosophila adult ovary [4]
In the posterior of the gonad, away from the terminal filaments, germline cells begin to express bam and show morphological signs of cyst development, while germline cells immediately adjacent to the terminal filament and newly established cap cells remain undifferentiated and express markers of Dpp signal responsiveness [42]. These cells, which probably give rise to adult GSCs, can undergo clonal expansion, giving rise to daughter GSCs that inhabit the same adult germarium. These findings suggest a simple model wherein primordial germ cell (PGC) immediately adjacent to cap cells receive bone morphogenetic protein (BMP) signals, continue to repress bam transcription and become incorporated into the maturing cap cell niche
Summary
Stem cells are essential for tissue homeostasis, in organs that exhibit high rates of cellular turnover such as the skin, intestine and hematopoietic system. In the posterior of the gonad, away from the terminal filaments, germline cells begin to express bam and show morphological signs of cyst development, while germline cells immediately adjacent to the terminal filament and newly established cap cells remain undifferentiated and express markers of Dpp signal responsiveness [42] These cells, which probably give rise to adult GSCs, can undergo clonal expansion, giving rise to daughter GSCs that inhabit the same adult germarium. The findings that shotgun and armadillo mutant PGCs within the developing gonad exhibit reduced interactions with newly formed cap cells [57] and the observation that Ecadherin contributes to the age-dependent decline of adult GSCs [58] highlight the importance of cell adhesion in promoting interactions between stem cells and their niches throughout life. The characterization of Lsd function in escort cells reveals that the active repression of niche-specific signals outside the normal microenvironment may be essential for proper tissue homeostasis in certain contexts
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