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  • 1
    Keywords: SURVIVAL ; CELL ; DEATH ; DIFFERENTIATION ; Drosophila ; CELL-DEATH ; TESTIS ; DISC ; cell death ; EXPANSION
    Type of Publication: Journal article epub ahead of print
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  • 2
    Abstract: A fundamental question is how complex structures are maintained after their initial specification. Stem cells reside in a specialized microenvironment, called niche, which provides essential signals controlling stem cell behavior. We addressed this question by studying the Drosophila male stem cell niche, called the hub. Once specified, the hub cells need to maintain their position and architectural integrity through embryonic, larval and pupal stages of testis organogenesis and during adult life. The Hox gene Abd-B, in addition to its described role in male embryonic gonads, maintains the architecture and positioning of the larval hub from the germline by affecting integrin localization in the neighboring somatic cyst cells. We find that the AbdB-Boss/Sev cascade affects integrin independent of Talin, while genetic interactions depict integrin as the central downstream player in this system. Focal adhesion and integrin-adaptor proteins within the somatic stem cells and cyst cells, such as Paxillin, Pinch and Vav, also contribute to proper hub integrity and positioning. During adult stages, hub positioning is controlled by Abd-B activity in the outer acto-myosin sheath, while Abd-B expression in adult spermatocytes exerts no effect on hub positioning and integrin localization. Our data point at a cell- and stage-specific function of Abd-B and suggest that the occurrence of new cell types and cell interactions in the course of testis organogenesis made it necessary to adapt the whole system by reusing the same players for male stem cell niche positioning and integrity in an alternative manner.
    Type of Publication: Journal article published
    PubMed ID: 26226434
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  • 3
    Keywords: EXPRESSION ; Germany ; REQUIREMENTS ; Drosophila ; MELANOGASTER ; EMBRYO ; LOCALIZATION ; EMBRYOS ; Drosophila melanogaster,pole cell migration,gonad formation,Scribble1,scribble,discs-large 1,lethal ; GERM-CELL MIGRATION ; NEUROTACTIN
    Type of Publication: Journal article published
    PubMed ID: 12711540
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  • 4
    Keywords: CELLS ; EXPRESSION ; proliferation ; SURVIVAL ; CELL ; Germany ; DEATH ; GENE ; PROTEIN ; DIFFERENTIATION ; TIME ; BIOLOGY ; AMPLIFICATION ; Drosophila ; CELL-DEATH ; REQUIRES ; spermatogenesis ; STEM-CELLS ; GERMLINE ; TESTIS ; OVEREXPRESSION ; TUMOR-SUPPRESSOR ; GERM-CELLS ; interaction ; development ; structure ; cell death ; RNAi ; USA ; SELF-RENEWAL ; STEM-CELL ; JUNCTION ; DIVISION ; Developmental ; SCC ; discs large ; SCRIBBLE ; somatic cyst cells ; SUPPORT CELLS ; testis formation
    Abstract: Gonad development requires a coordinated soma-germline interaction that ensures renewal and differentiation of germline and somatic stem cells to ultimately produce mature gametes. The Drosophila tumour suppressor gene discs large (dlg) encodes a septate junction protein functioning during epithelial polarization, asymmetric neuroblast division, and formation of neuromuscular junctions. Here, we report the role of dlg in testis development and its critical function in somatic cyst cells (SCCs). In these cells dlg is primarily required for their survival and expansion, and contributes to spermatocyte cyst differentiation. Cell death primarily occurred in SCCs at the end of spermatogonial amplification at a time when Dlg becomes restricted in wild-type (wt) testes to the distal somatic cells capping the growing spermatocyte cysts. RNAi depletion of dlg transcripts in early SCCs fully prevented testis development, whereas depletion in late SCCs resulted in a breakdown of spermatocyte cyst structure and germ cell individualization. Specific dlg expression in SCCs resulted in developmental rescue of dlg mutant testes, whereas its expression in germ cells exerted no such effect. dlg overexpression in wt testes led to spermatocyte cyst expansion at the expense of spermatogonial cysts. Our data demonstrate that dlg is essentially required in SCCs for their survival, expansion, and differentiation, and for the encapsulation of the germline cells
    Type of Publication: Journal article published
    PubMed ID: 19546890
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  • 5
    Keywords: APOPTOSIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; DEATH ; DISEASE ; GENE ; PROTEIN ; transcription ; DIFFERENTIATION ; MECHANISM ; METASTASIS ; genetics ; CANCER-CELLS ; CANCER-RESEARCH ; PROGRAMMED CELL-DEATH ; MULTIPLE ROLES ; NOTCH ; ACTS ; GENETIC SCREEN ; REAPER ; WING-MARGIN
    Abstract: Apoptosis is essential to prevent oncogenic transformation by triggering self-destruction of harmful cells, including those unable to differentiate. However, the mechanisms linking impaired cell differentiation and apoptosis during development and disease are not well understood. Here we report that the Drosophila transcription factor Cut coordinately controls differentiation and repression of apoptosis via direct regulation of the pro-apoptotic gene reaper. We also demonstrate that this regulatory circuit acts in diverse cell lineages to remove uncommitted precursor cells in status nascendi and thereby interferes with their potential to develop into cancer cells. Consistent with the role of Cut homologues in controlling cell death in vertebrates, we find repression of apoptosis regulators by Cux1 in human cancer cells. Finally, we present evidence that suggests that other lineage-restricted specification factors employ a similar mechanism to put the brakes on the oncogenic process
    Type of Publication: Journal article published
    PubMed ID: 22438831
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  • 6
    Keywords: PROTEIN ; GERM-CELLS ; centrosome ; SRC FAMILY KINASES ; F-ACTIN ; SELF-RENEWAL ; BITHORAX COMPLEX ; HEMATOPOIETIC STEM ; ABDOMINAL-B ; LAMININ-A
    Abstract: Proper niche architecture is critical for stem cell function, yet only few upstream regulators are known. Here, we report that the Hox transcription factor Abdominal-B (Abd-B), active in premeiotic spermatocytes of Drosophila testes, is essential for positioning the niche to the testis anterior by regulating integrin in neighboring somatic cyst cells. Abd-B also non-cell-autonomously controls critical features within the niche, including centrosome orientation and division rates of germline stem cells. By using genome-wide binding studies, we find that Abd-B mediates its effects on integrin localization by directly controlling at multiple levels the signaling activity of the Sev ligand Boss via its direct targets src42A and sec63, two genes involved in protein trafficking and recycling. Our data show that Abd-B, through local signaling between adjucent cell types, provides positional cues for integrin localization, which is critical for placement of the distant stem cell niche and stem cell activity.
    Type of Publication: Journal article published
    PubMed ID: 24480643
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  • 7
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    Fly 4 (4), 294-298 
    Abstract: Gamete development requires a coordinated soma-germ line interaction that ensures renewal and differentiation of germline and somatic stem cells. The physical contact between the germline and somatic cell populations is crucial because it allows the exchange of diffusible signals among them. The tumor suppressor gene discs large (dlg) encodes a septate junction protein with functions in epithelial cell polarity, asymmetric neuroblast division and formation of neuromuscular junctions. Our recent work reveals a new role of dig in the Drosophila testis, as mutations in dlg lead to testis defects and cell death. Dlg is required throughout spermatogenesis in the somatic lineage and its localization changes from a uniform distribution along the plasma membrane of somatic cells in the testis apex, to a restricted localization on the distally located somatic cell in growing cysts. The extensive defects in dig testis underline the importance of the somatic cells in the establishment and maintenance of the male stem cell niche and somatic cell differentiation. Here, we discuss our latest findings on the role of dlg in the Drosophila testis, supporting the view that junction proteins are dynamic structures, which can provide guiding cues to recruit scaffold proteins or other signaling molecules
    Type of Publication: Journal article published
    PubMed ID: 20798604
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