Rap-GEF Signaling Controls Stem Cell Anchoring to Their Niche through Regulating DE-Cadherin-Mediated Cell Adhesion in the Drosophila Testis

Wang, Hong; Singh, Shree Ram; Zheng, Zhiyu; Oh, Su-Wan; Chen, Xiu; Edwards, Kevin A.; Hou, Steven X.

doi:10.1016/j.devcel.2005.11.004

Cited by 94 publications

(92 citation statements)

References 37 publications

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“…In this, they may be analogous to the hub cells present in the Drosophila gonadal niches where cell-cell interaction between hub and stem cell are required to maintain the latter in an undifferentiated state, in the SEZ providing signals that cannot be transmitted via the basal process [18,19]. However, our observations do not argue against conclusions from recent experimental work that the vasculature plays a critical role in supporting stem/ precursor cell proliferation [4][5][6].…”

Section: Kazanis and Ffrench-constantmentioning

confidence: 45%

The Number of Stem Cells in the Subependymal Zone of the Adult Rodent Brain is Correlated with the Number of Ependymal Cells and Not with the Volume of the Niche

Kazanis

ffrench‐Constant

2012

Stem Cells and Development

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2The mammalian subependymal zone (SEZ; often called subventricular) situated at the lateral walls of the lateral ventricles of the brain contains a pool of relatively quiescent adult neural stem cells whose neurogenic activity persists throughout life. These stem cells are positioned in close proximity both to the ependymal cells that provide the cerebrospinal fluid interface and to the blood vessel endothelial cells, but the relative contribution of these 2 cell types to stem cell regulation remains undetermined. Here, we address this question by analyzing a naturally occurring example of volumetric scaling of the SEZ in a comparison of the mouse SEZ with the larger rat SEZ. Our analysis reveals that the number of stem cells in the SEZ niche is correlated with the number of ependymal cells rather than with the volume, thereby indicating the importance of ependymal-derived factors in the formation and function of the SEZ. The elucidation of the factors generated by ependymal cells that regulate stem cell numbers within the SEZ is, therefore, of importance for stem cell biology and regenerative neuroscience.

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Section: Kazanis and Ffrench-constantmentioning

confidence: 45%

The Number of Stem Cells in the Subependymal Zone of the Adult Rodent Brain is Correlated with the Number of Ependymal Cells and Not with the Volume of the Niche

Kazanis

ffrench‐Constant

2012

Stem Cells and Development

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“…S7a), suggesting that BMP pathway activity in GSCs was lost before detachment from the hub. Interfering with the cadherin-trafficking machinery in ligand-producing cells therefore affects niche function before the receiving cells drift out of signal range 13,14,33 . Strikingly, mutations in Gef26/dizzy, an activator of the small GTPase Rap1 that is involved in junction maintenance 38 , also affect both cadherin localization in the hub and niche signalling 14 .…”

Section: Generation Of the Local Bmp Niche Signal Transmission Of Ovmentioning

confidence: 99%

“…Consequently, GSCs begin to express Bam and lose stem cell fate when they are displaced from the hub following a loss of Cadherinmediated adhesion 13,14 or are outcompeted by CySCs with increased adhesiveness 15 . Thus, a direct BMP signal from the hub cells is likely to be required for GSC maintenance.…”

mentioning

confidence: 99%

Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche

et al. 2011

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According to the stem cell niche synapse hypothesis postulated for the mammalian haematopoietic system, spatial specificity of niche signals is maximized by subcellularly restricting signalling to cadherin-based adherens junctions between individual niche and stem cells. However, such a synapse has never been observed directly, in part, because tools to detect active growth factor receptors with subcellular resolution were not available. Here we describe a novel fluorescence-based reporter that directly visualizes bone morphogenetic protein (BmP) receptor activation and show that in the Drosophila testis a BmP niche signal is transmitted preferentially at adherens junctions between hub and germline stem cells, resembling the proposed synapse organization. Ligand secretion involves the exocyst complex and the Rap activator Gef26, both of which are also required for Cadherin trafficking towards adherens junctions. We, therefore, propose that local generation of the BmP signal is achieved through shared use of the Cadherin transport machinery.

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“…E-Cad is an integral component of the adherens junctions that maintain GSC fate in adults by ensuring physical contact between GSCs and the niche and that polarize GSC divisions perpendicular to the hub (77,83,84). Drosophila gef26 encodes a guanine nucleotide exchange factor for the Rap guanine triphosphatase (GTPase) pathway that localizes to the hub-GSC interface (93,94). In gef26 mutants, the hub is specified normally, but GSC fate is not maintained because of the absence of adherens junctions between hub cells and GSCs (93).…”

Section: And Ref 83)mentioning

confidence: 99%

“…Drosophila gef26 encodes a guanine nucleotide exchange factor for the Rap guanine triphosphatase (GTPase) pathway that localizes to the hub-GSC interface (93,94). In gef26 mutants, the hub is specified normally, but GSC fate is not maintained because of the absence of adherens junctions between hub cells and GSCs (93). Experiments in mammalian cell culture and Drosophila epithelia indicated a direct role for the Rap pathway in localizing E-Cad to newly formed intercellular contact sites, facilitating the development of mature adherens junctions (95,96).…”

Section: And Ref 83)mentioning

confidence: 99%

The Development of Germline Stem Cells in Drosophila

Dansereau

Lasko

2008

Methods in Molecular Biology™

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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...

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Rap-GEF Signaling Controls Stem Cell Anchoring to Their Niche through Regulating DE-Cadherin-Mediated Cell Adhesion in the Drosophila Testis

Cited by 94 publications

References 37 publications

The Number of Stem Cells in the Subependymal Zone of the Adult Rodent Brain is Correlated with the Number of Ependymal Cells and Not with the Volume of the Niche

The Number of Stem Cells in the Subependymal Zone of the Adult Rodent Brain is Correlated with the Number of Ependymal Cells and Not with the Volume of the Niche

Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche

The Development of Germline Stem Cells in Drosophila

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