scholarly journals Phagocytosis genes nonautonomously promote developmental cell death in the Drosophila ovary

2016 ◽  
Vol 113 (9) ◽  
pp. E1246-E1255 ◽  
Author(s):  
Allison K. Timmons ◽  
Albert A. Mondragon ◽  
Claire E. Schenkel ◽  
Alla Yalonetskaya ◽  
Jeffrey D. Taylor ◽  
...  
Keyword(s):  
Cell Death ◽  
Large Scale ◽  
Germ Line ◽  
Follicle Cells ◽  
Small Subset ◽  
Nurse Cells ◽  
Cell Death Program ◽  
Cell Death Mechanisms ◽  
Developmental Cell Death ◽  
Drosophila Ovary

Programmed cell death (PCD) is usually considered a cell-autonomous suicide program, synonymous with apoptosis. Recent research has revealed that PCD is complex, with at least a dozen cell death modalities. Here, we demonstrate that the large-scale nonapoptotic developmental PCD in the Drosophila ovary occurs by an alternative cell death program where the surrounding follicle cells nonautonomously promote death of the germ line. The phagocytic machinery of the follicle cells, including Draper, cell death abnormality (Ced)-12, and c-Jun N-terminal kinase (JNK), is essential for the death and removal of germ-line–derived nurse cells during late oogenesis. Cell death events including acidification, nuclear envelope permeabilization, and DNA fragmentation of the nurse cells are impaired when phagocytosis is inhibited. Moreover, elimination of a small subset of follicle cells prevents nurse cell death and cytoplasmic dumping. Developmental PCD in the Drosophila ovary is an intriguing example of nonapoptotic, nonautonomous PCD, providing insight on the diversity of cell death mechanisms.

scholarly journals Murder on the Ovarian Express: A Tale of Non-Autonomous Cell Death in the Drosophila Ovary

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1454
Author(s):  
Diane Patricia Vig Lebo ◽  
Kimberly McCall
Keyword(s):  
Cell Death ◽  
Follicle Cells ◽  
Nurse Cells ◽  
Fine Line ◽  
Egg Chambers ◽  
Drosophila Ovary ◽  
Size And Structure

Throughout oogenesis, Drosophila egg chambers traverse the fine line between survival and death. After surviving the ten early and middle stages of oogenesis, egg chambers drastically change their size and structure to produce fully developed oocytes. The development of an oocyte comes at a cost, the price is the lives of the oocyte’s 15 siblings, the nurse cells. These nurse cells do not die of their own accord. Their death is dependent upon their neighbors—the stretch follicle cells. Stretch follicle cells are nonprofessional phagocytes that spend the final stages of oogenesis surrounding the nurse cells and subsequently forcing the nurse cells to give up everything for the sake of the oocyte. In this review, we provide an overview of cell death in the ovary, with a focus on recent findings concerning this phagocyte-dependent non-autonomous cell death.

Different 3′ untranslated regions target alternatively processed hu-li tai shao (hts) transcripts to distinct cytoplasmic locations during Drosophila oogenesis

1999 ◽  
Vol 112 (19) ◽  
pp. 3385-3398 ◽  
Author(s):  
K.L. Whittaker ◽  
D. Ding ◽  
W.W. Fisher ◽  
H.D. Lipshitz
Keyword(s):  
Germ Line ◽  
Protein Isoforms ◽  
Follicle Cells ◽  
Untranslated Regions ◽  
Nurse Cells ◽  
Anterior Pole ◽  
Amino Terminal ◽  
Alternative Processing ◽  
Carboxy Terminal ◽  
Drosophila Ovary

Cytoplasmic mRNA localization is one method by which protein production is restricted to a particular intracellular site. We report here a novel mechanism for localization of transcripts encoding distinct protein isoforms to different destinations. Alternative processing of transcripts produced in the Drosophila ovary by the hu-li tai shao (hts) locus introduces distinct 3′ untranslated regions (3′UTRs) that differentially localize the mRNAs. Three classes of hts mRNA (R2, N32 and N4) are synthesized in the germ line nurse cells and encode proteins with adducin-homologous amino-terminal regions but divergent carboxy-terminal domains. The R2 and N32 classes of mRNA remain in the nurse cells and are not transported into the oocyte. In contrast, the N4 class of transcripts is transported from the nurse cells into the oocyte starting at stage 1, is subsequently localized to the oocyte cortex at stage 8 and then to the anterior pole from stage 9 on. All aspects of N4 transcript transport and localization are directed by the 345-nucleotide(nt)-long 3′ untranslated region (3′UTR). The organization of localization elements in the N4 3′UTR is modular: a 150 nt core is sufficient to direct transport and localization throughout oogenesis. Additional 3′UTR elements function additively together with this core region at later stages of oogenesis to maintain or enhance anterior transcript anchoring. The swallow locus is required to maintain hts transcripts at the anterior pole of the oocyte and functions through the N4 3′UTR. In addition to the three classes of germ line-expressed hts transcripts, a fourth class (R1) is expressed in the somatic follicle cells that surround the germ line cells. This transcript class encodes the Drosophila orthologue of mammalian adducin.

Infection of the germ line by retroviral particles produced in the follicle cells: a possible mechanism for the mobilization of the gypsy retroelement of Drosophila

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2789-2798 ◽  
Author(s):  
S.U. Song ◽  
M. Kurkulos ◽  
J.D. Boeke ◽  
V.G. Corces
Keyword(s):  
High Frequency ◽  
Cytoplasmic Membrane ◽  
De Novo ◽  
Germ Line ◽  
High Rate ◽  
Follicle Cells ◽  
Nurse Cells ◽  
Perivitelline Space ◽  
Viral Particles ◽  
Secretory Apparatus

The gypsy retroelement of Drosophila moves at high frequency in the germ line of the progeny of females carrying a mutation in the flamenco (flam) gene. This high rate of de novo insertion correlates with elevated accumulation of full-length gypsy RNA in the ovaries of these females, as well as the presence of an env-specific RNA. We have prepared monoclonal antibodies against the gypsy Pol and Env products and found that these proteins are expressed in the ovaries of flam females and processed in the manner characteristic of vertebrate retroviruses. The Pol proteins are expressed in both follicle and nurse cells, but they do not accumulate at detectable levels in the oocyte. The Env proteins are expressed exclusively in the follicle cells starting at stage 9 of oogenesis, where they accumulate in the secretory apparatus of the endoplasmic reticulum. They then migrate to the inner side of the cytoplasmic membrane where they assemble into viral particles. These particles can be observed in the perivitelline space starting at stage 10 by immunoelectron microscopy using anti-Env antibodies. We propose a model to explain flamenco-mediated induction of gypsy mobilization that involves the synthesis of gypsy viral particles in the follicle cells, from where they leave and infect the oocyte, thus explaining gypsy insertion into the germ line of the subsequent generation.

scholarly journals PolyQ disease: misfiring of a developmental cell death program?

2013 ◽  
Vol 23 (4) ◽  
pp. 168-174 ◽  
Author(s):  
Elyse S. Blum ◽  
Andrew R. Schwendeman ◽  
Shai Shaham
Keyword(s):  
Cell Death ◽  
Polyq Disease ◽  
Cell Death Program ◽  
Developmental Cell Death

scholarly journals Cell death in animal development

Development ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. dev191882
Author(s):  
Piya Ghose ◽  
Shai Shaham
Keyword(s):  
Cell Death ◽  
Normal Development ◽  
Physical Injury ◽  
Developmental Abnormalities ◽  
Animal Development ◽  
Evolutionary Selection ◽  
Different Types ◽  
Cell Death Mechanisms ◽  
Ultimate Fate ◽  
Developmental Cell Death

ABSTRACTCell death is an important facet of animal development. In some developing tissues, death is the ultimate fate of over 80% of generated cells. Although recent studies have delineated a bewildering number of cell death mechanisms, most have only been observed in pathological contexts, and only a small number drive normal development. This Primer outlines the important roles, different types and molecular players regulating developmental cell death, and discusses recent findings with which the field currently grapples. We also clarify terminology, to distinguish between developmental cell death mechanisms, for which there is evidence for evolutionary selection, and cell death that follows genetic, chemical or physical injury. Finally, we suggest how advances in understanding developmental cell death may provide insights into the molecular basis of developmental abnormalities and pathological cell death in disease.

Apoptosis-based therapies for hematologic malignancies

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 408-418 ◽  
Author(s):  
John C. Reed ◽  
Maurizio Pellecchia
Keyword(s):  
Cell Death ◽  
Hematopoietic Cells ◽  
Hematologic Malignancies ◽  
Cell Turnover ◽  
New Therapies ◽  
The Core ◽  
Cell Death Program ◽  
Core Components ◽  
Cell Death Mechanisms ◽  
Structural Levels

Abstract Apoptosis is an intrinsic cell death program that plays critical roles in tissue homeostasis, especially in organs where high rates of daily cell production are offset by rapid cell turnover. The hematopoietic system provides numerous examples attesting to the importance of cell death mechanisms for achieving homeostatic control. Much has been learned about the mechanisms of apoptosis of lymphoid and hematopoietic cells since the seminal observation in 1980 that glucocorticoids induce DNA fragmentation and apoptosis of thymocytes and the demonstration in 1990 that depriving colony-stimulating factors from factor-dependent hematopoietic cells causes programmed cell death. From an understanding of the core components of the apoptosis machinery at the molecular and structural levels, many potential new therapies for leukemia and lymphoma are emerging. In this review, we introduce some of the drug discovery targets thus far identified within the core apoptotic machinery and describe some of the progress to date toward translating our growing knowledge about these targets into new therapies for cancer and leukemia.

scholarly journals An RNAi screen of the kinome in epithelial follicle cells of the Drosophila melanogaster ovary reveals genes required for proper germline death and clearance

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Diane P V Lebo ◽  
Alice Chirn ◽  
Jeffrey D Taylor ◽  
Andre Levan ◽  
Valentina Doerre Torres ◽  
...  
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Follicle Cells ◽  
Multiple Time ◽  
Cell Clearance ◽  
Germline Cells ◽  
Multiple Time Points ◽  
Cell Corpse ◽  
Cell Corpse Clearance ◽  
Drosophila Ovary

Abstract Programmed cell death and cell corpse clearance are an essential part of organismal health and development. Cell corpses are often cleared away by professional phagocytes such as macrophages. However, in certain tissues, neighboring cells known as nonprofessional phagocytes can also carry out clearance functions. Here, we use the Drosophila melanogaster ovary to identify novel genes required for clearance by nonprofessional phagocytes. In the Drosophila ovary, germline cells can die at multiple time points. As death proceeds, the epithelial follicle cells act as phagocytes to facilitate the clearance of these cells. We performed an unbiased kinase screen to identify novel proteins and pathways involved in cell clearance during two death events. Of 224 genes examined, 18 demonstrated severe phenotypes during developmental death and clearance while 12 demonstrated severe phenotypes during starvation-induced cell death and clearance, representing a number of pathways not previously implicated in phagocytosis. Interestingly, it was found that several genes not only affected the clearance process in the phagocytes, but also non-autonomously affected the process by which germline cells died. This kinase screen has revealed new avenues for further exploration and investigation.

scholarly journals Autophagy in Cancer Cell Death

Biology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 82 ◽  
Author(s):  
Linder ◽  
Kögel
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Drug Induced ◽  
Cancer Cell Death ◽  
Cell Death Program ◽  
Cellular Context ◽  
Dependent Cell ◽  
Developmental Cell Death ◽  
Cellular Components

Autophagy has important functions in maintaining energy metabolism under conditions of starvation and to alleviate stress by removal of damaged and potentially harmful cellular components. Therefore, autophagy represents a pro-survival stress response in the majority of cases. However, the role of autophagy in cell survival and cell death decisions is highly dependent on its extent, duration, and on the respective cellular context. An alternative pro-death function of autophagy has been consistently observed in different settings, in particular, in developmental cell death of lower organisms and in drug-induced cancer cell death. This cell death is referred to as autophagic cell death (ACD) or autophagy-dependent cell death (ADCD), a type of cellular demise that may act as a backup cell death program in apoptosis-deficient tumors. This pro-death function of autophagy may be exerted either via non-selective bulk autophagy or excessive (lethal) removal of mitochondria via selective mitophagy, opening new avenues for the therapeutic exploitation of autophagy/mitophagy in cancer treatment.

scholarly journals Vps13 is required for timely removal of nurse cell corpses

Development ◽  
2020 ◽  
Vol 147 (20) ◽  
pp. dev191759
Author(s):  
Anita I. E. Faber ◽  
Marianne van der Zwaag ◽  
Hein Schepers ◽  
Ellie Eggens-Meijer ◽  
Bart Kanon ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Programmed Cell Death ◽  
Nurse Cell ◽  
Close Association ◽  
Follicle Cells ◽  
Nurse Cells ◽  
Lipid Transfer ◽  
Membranous Structure ◽  
Membrane Contact Sites

ABSTRACTProgrammed cell death and consecutive removal of cellular remnants is essential for development. During late stages of Drosophila melanogaster oogenesis, the small somatic follicle cells that surround the large nurse cells promote non-apoptotic nurse cell death, subsequently engulf them, and contribute to the timely removal of nurse cell corpses. Here, we identify a role for Vps13 in the timely removal of nurse cell corpses downstream of developmental programmed cell death. Vps13 is an evolutionarily conserved peripheral membrane protein associated with membrane contact sites and lipid transfer. It is expressed in late nurse cells, and persistent nurse cell remnants are observed when Vps13 is depleted from nurse cells but not from follicle cells. Microscopic analysis revealed enrichment of Vps13 in close proximity to the plasma membrane and the endoplasmic reticulum in nurse cells undergoing degradation. Ultrastructural analysis uncovered the presence of an underlying Vps13-dependent membranous structure in close association with the plasma membrane. The newly identified structure and function suggests the presence of a Vps13-dependent process required for complete degradation of bulky remnants of dying cells.

Cell death in ovarian chambers of Drosophila melanogaster

Development ◽  
1976 ◽  
Vol 35 (3) ◽  
pp. 521-533
Author(s):  
F. Giorgi ◽  
P. Deri
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Morphological Change ◽  
Current Literature ◽  
Normal Development ◽  
Nuclear Material ◽  
Ultrastructural Analysis ◽  
Follicle Cells ◽  
Nurse Cells ◽  
Cell Cytoplasm

An ultrastructural analysis has been made of certain ovarian chambers undergoing ab-normal development. The earliest morphological change in these chambers consists of thealteration of the nuclear material which is then followed by engulfment of portions of thenurse cell cytoplasm, including the nuclear fragments, into the overlying follicle cells. Thecontinuation of this process leads to the progressive disappearance of nurse cells with theconcomitant formation of huge dense vacuoles in the follicle layer. The morphological featuresdescribed in the present investigation are similar to those found in other tissues and inter-preted as leading to cell death. It is suggested that certain ovarian chambers undergo celldeath as a result of the incapability of furthering their development. The role played by celldeath in oogenesis is also discussed on the basis of the current literature.

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