The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis

Papagiannouli, Fani; Berry, Cameron W.; Fuller, Margaret T.

doi:10.1016/j.stemcr.2019.03.008

Cited by 23 publications

(26 citation statements)

References 53 publications

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“…6A). Transcripts encoding cell junction proteins were downregulated, in keeping with previous reports showing that expression of septate and adherens junction components increases during cyst cell differentiation (Dubey et al, 2019;Fairchild et al, 2017;Fairchild et al, 2015;Papagiannouli et al, 2019). A large number of downregulated transcripts encoded genes involved in various aspects of oxidative metabolism and ATP production (Fig.…”

Section: Ectopic E2f1/dp Activity In Cyscs Alters Expression Of Genessupporting

confidence: 88%

Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Maza

Hof-Michel

Phillimore

et al. 2021

Preprint

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Stem cells maintain tissue homeostasis by proliferating to replace cells lost to damage or natural turnover. Whereas stem and progenitor cells proliferate, fully differentiated cells exit the cell cycle. How cell identity and cell cycle state are coordinated during this process is still poorly understood. The Drosophila testis niche supports germline stem cells and somatic cyst stem cells (CySCs), which are the only proliferating somatic cells in the testis. CySCs give rise to post-mitotic cyst cells and therefore provide a tractable model to ask how stem cell identity is linked to proliferation. We show that the G1/S cyclin, Cyclin E, is required for CySC self-renewal; however, its canonical transcriptional regulator, a complex of the E2f1 and Dp transcription factors is dispensable for self-renewal and cell cycle progression. Nevertheless, we demonstrate that E2f1/Dp activity must be silenced to allow CySCs to differentiate. We show that E2f1/Dp activity inhibits the expression of genes important for mitochondrial activity. Furthermore, promoting mitochondrial activity or biogenesis is sufficient to rescue the differentiation of CySCs with ectopic E2f1/Dp activity but not their exit from the cell cycle. Our findings together indicate that E2f1/Dp coordinates cell cycle progression with stem cell identity by regulating the metabolic state of CySCs.

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Section: Ectopic E2f1/dp Activity In Cyscs Alters Expression Of Genessupporting

confidence: 88%

Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Maza

Hof-Michel

Phillimore

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Somatic cells are required to encapsulate germ cells for differentiation 14 . Several studies have demonstrated the roles of EGFR signaling in germline differentiation via EGFR, Ras, and Raf factors 23 , 26 , 42 , 44 . However, the role of Dsor1 and rl in the homeostasis of the stem cell niche in the Drosophila testis was not extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Somatic CG6015 mediates cyst stem cell maintenance and germline stem cell differentiation via EGFR signaling in Drosophila testes

et al. 2021

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Stem cell niche is regulated by intrinsic and extrinsic factors. In the Drosophila testis, cyst stem cells (CySCs) support the differentiation of germline stem cells (GSCs). However, the underlying mechanisms remain unclear. In this study, we found that somatic CG6015 is required for CySC maintenance and GSC differentiation in a Drosophila model. Knockdown of CG6015 in CySCs caused aberrant activation of dpERK in undifferentiated germ cells in the Drosophila testis, and disruption of key downstream targets of EGFR signaling (Dsor1 and rl) in CySCs results in a phenotype resembling that of CG6015 knockdown. CG6015, Dsor1, and rl are essential for the survival of Drosophila cell line Schneider 2 (S2) cells. Our data showed that somatic CG6015 regulates CySC maintenance and GSC differentiation via EGFR signaling, and inhibits aberrant activation of germline dpERK signals. These findings indicate regulatory mechanisms of stem cell niche homeostasis in the Drosophila testis.

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“…Signalling via the epidermal growth factor receptor (EGFR) in somatic cyst cells has also been shown to be regulated by the Discs large 1, Scribble and Lethal (2) giant larvae proteins. The three SJ proteins cooperate with clathrin‐mediated endocytic components to downregulate EGFR, and this interplay ensures the establishment of a functional cyst microenvironment that supports the survival of differentiating germ cells 32 . Similarly, inhibition of the EGFR signalling pathway has been documented in the Drosophila eye through the interaction of the SJ protein Neuroglian with the cell adhesion molecule echinoid.…”

Section: Current Evidence and Integration Of Findingsmentioning

confidence: 99%

“…Table 1 presents all genes encoding the aforementioned proteins and their corresponding UniprotKB and FlyBase IDs, with the relevant references 3,5,17‐91 …”

Section: Current Evidence and Integration Of Findingsmentioning

confidence: 99%

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families

et al. 2020

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The involvement of Septate Junctions (SJs) in critical cellular functions that extend beyond their role as diffusion barriers in the epithelia and the nervous system has made the fruit fly an ideal model for the study of human diseases associated with impaired Tight Junction (TJ) function. In this study, we summarized current knowledge of the Drosophila melanogaster SJ‐related proteins, focusing on their unconventional functions. Additionally, we sought to identify human orthologs of the corresponding genes as well as protein domain families. The systematic literature search was performed in PubMed and Scopus databases using relevant key terms. Orthologs were predicted using the DIOPT tool and aligned protein regions were determined from the Pfam database. 3‐D models of the smooth SJ proteins were built on the Phyre2 and DMPFold protein structure prediction servers. A total of 30 proteins were identified as relatives to the SJ cellular structure. Key roles of these proteins, mainly in the regulation of morphogenetic events and cellular signalling, were highlighted. The investigation of protein domain families revealed that the SJ‐related proteins contain conserved domains that are required not only for cell‐cell interactions and cell polarity but also for cellular signalling and immunity. DIOPT analysis of orthologs identified novel human genes as putative functional homologs of the fruit fly SJ genes. A gap in our knowledge was identified regarding the domains that occur in the proteins encoded by eight SJ‐associated genes. Future investigation of these domains is needed to provide functional information.

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The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis

Cited by 23 publications

References 53 publications

Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Somatic CG6015 mediates cyst stem cell maintenance and germline stem cell differentiation via EGFR signaling in Drosophila testes

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families

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