I Spy in the Developing Fly a Multitude of Ways to Die

Cell proliferation and cell death are two opposing, yet complementary fundamental processes in development. Cell proliferation provides new cells, while developmental programmed cell death adjusts cell numbers and refines structures as an organism grows. Apoptosis is the best-characterized form of programmed cell death; however, there are many other non-apoptotic forms of cell death that occur throughout development. Drosophila is an excellent model for studying these varied forms of cell death given the array of cellular, molecular, and genetic techniques available. In this review, we discuss select examples of apoptotic and non-apoptotic cell death that occur in different tissues and at different stages of Drosophila development. For example, apoptosis occurs throughout the nervous system to achieve an appropriate number of neurons. Elsewhere in the fly, non-apoptotic modes of developmental cell death are employed, such as in the elimination of larval salivary glands and midgut during metamorphosis. These and other examples discussed here demonstrate the versatility of Drosophila as a model organism for elucidating the diverse modes of programmed cell death.

Download Full-text

miR-103 Functions as a Tumor Suppressor by Directly Targeting Programmed Cell Death 10 in NSCLC

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15000757094686 ◽

2018 ◽

Vol 26 (4) ◽

pp. 519-528 ◽

Cited By ~ 10

Author(s):

Dong Yang ◽

Jian-Jun Wang ◽

Jin-Song Li ◽

Qian-Yu Xu

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Death ◽

Programmed Cell Death ◽

Tumor Size ◽

Apoptotic Cell ◽

A549 Cells ◽

Invasion And Migration ◽

Metastatic Capacity ◽

And Migration

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Absence of miR-103 has recently been identified to be associated with metastatic capacity of primary lung tumors. However, the exact role of miR-103 in NSCLC and the molecular mechanism are unclear. In the present study, we showed that miR-103 expression was reduced in NSCLC tissues and cells. miR-103 expression was negatively correlated with tumor size and stage. The overall survival was longer in patients with higher miR-103 level than in those with lower miR-103 expression. miR-103 inhibited cell proliferation in A549 cells, decreased tumor weight and volume, and prolonged survival of tumor-implanted nude mice. miR-103 increased apoptotic cell death in A549 cells. Furthermore, miR-103 decreased the invasion and migration abilities in A549 cells, as evidenced by Transwell and wound healing results. Downregulation of miR-103 significantly reduced the level of programmed cell death 10 (PDCD10). We found a significant decrease in the relative luciferase activity of the reporter gene in A549 cells cotransfected with the miR-103 mimic and pGL3-PDCD10 WT 3′-UTR, but not pGL3-PDCD10 mut 3′-UTR. We showed that overexpression of PDCD10 significantly inhibited miR-103-induced inhibition of cell proliferation, increased apoptosis, and decreased invasion and migration in A549 cells. Moreover, we found that PDCD10 expression was increased in NSCLC tissues and cells. PDCD10 expression was positively correlated with tumor size and stage. Overexpression of PDCD10 increased cell proliferation and inhibited apoptosis in A549 cells. The data demonstrated that dysregulation of the miR-103/PDCD10 signal may be a novel therapeutic target for the treatment of NSCLC.

Download Full-text

Mesenchymal cell proliferation and programmed cell death: key players in fibrogenesis and new targets for therapeutic intervention

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00504.2010 ◽

2011 ◽

Vol 300 (5) ◽

pp. G703-G708 ◽

Cited By ~ 8

Author(s):

Jeroni Luna ◽

Maria Carme Masamunt ◽

Ian Craig Lawrance ◽

Miquel Sans

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Programmed Cell Death ◽

Mesenchymal Cell ◽

Limited Attention ◽

Intestinal Fibrosis ◽

Proliferation And Apoptosis ◽

Physiological Homeostasis ◽

Inflammatory Bowel ◽

Different Tissues

An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and especially in Crohn's disease, enhanced proliferation along with defective apoptosis of immune cells are considered key elements of pathogenesis. Despite the relatively limited attention that has been given to research efforts devoted to intestinal fibrosis to date, there is evidence suggesting that enhanced proliferation along with defective programmed cell death of mesenchymal cells can significantly contribute to the development of excessive fibrogenesis in many different tissues. Moreover, some therapies have demonstrated potential antifibrogenic efficacy through the regulation of mesenchymal cell proliferation and programmed cell death. Further understanding of the pathways involved in the regulation of mesenchymal cell proliferation and apoptosis is, however, required.

Download Full-text

Mutations affecting neural survival in the zebrafish Danio rerio

Development ◽

10.1242/dev.123.1.217 ◽

1996 ◽

Vol 123 (1) ◽

pp. 217-227 ◽

Cited By ~ 5

Author(s):

S. Abdelilah ◽

E. Mountcastle-Shah ◽

M. Harvey ◽

L. Solnica-Krezel ◽

A.F. Schier ◽

...

Keyword(s):

Central Nervous System ◽

Cell Death ◽

Nervous System ◽

Programmed Cell Death ◽

Danio Rerio ◽

Apoptotic Cell ◽

Brain Morphology ◽

Genetic Components ◽

The Central Nervous System ◽

Dying Cells

Programmed cell death is a prominent feature of normal animal development. During neurogenesis, naturally occurring cell death is a mechanism to eliminate neurons that fail to make appropriate connections. To prevent accidental cell death, mechanisms that trigger programmed cell death, as well as the genetic components of the cell death program, are tightly controlled. In a large-scale mutagenesis screen for embryonic lethal mutations in zebrafish Danio rerio we have found 481 mutations with a neural degeneration phenotype. Here, we present 50 mutations that fall into two classes (termed spacehead and fala-like) that are characterized by two main features: first, they appear to affect cell survival primarily within the neuroectodermal lineages during somitogenesis, and second, they show an altered brain morphology at or before 28 hours of development. Evidence for the specificity of cell death within the central nervous system comes from visual inspection of dying cells and analysis of DNA fragmentation, a process associated with apoptotic cell death. In mutants, the level of dying cells is significantly increased in brain and spinal cord. Furthermore, at the end of somitogenesis, the cell count of radial glia and trigeminal neurons is reduced in some mutants of the spacehead class. A variety of neurodegenerative disorders in mouse and humans have been associated with abnormal levels of programmed cell death within the central nervous system. The mutations presented here might provide a genetic framework to aid in the understanding of the etiology of degenerative and physiological disorders within the CNS and the activation of inappropriate programmed cell death.

Download Full-text

Faculty Opinions recommendation of Programmed cell death in the embryonic central nervous system of Drosophila melanogaster.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1065954.518915 ◽

2007 ◽

Author(s):

Marc Freeman

Keyword(s):

Central Nervous System ◽

Cell Death ◽

Nervous System ◽

Drosophila Melanogaster ◽

Programmed Cell Death

Download Full-text

Receptor Tyrosine Kinases: Role in Cancer Progression

Current Oncology ◽

10.3390/curroncol13050019 ◽

2006 ◽

Vol 13 (5) ◽

pp. 191-193

Author(s):

V. Sangwan ◽

M. Park

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Programmed Cell Death ◽

Cancer Progression ◽

Tyrosine Kinases ◽

Normal Tissue ◽

Receptor Tyrosine Kinases ◽

Tight Control ◽

Tissue Patterning

Tight control of cell proliferation and morphogenesis in conjunction with programmed cell death (apoptosis) is required to ensure normal tissue patterning. [...]

Download Full-text

Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00406.2000 ◽

2002 ◽

Vol 282 (3) ◽

pp. L477-L483 ◽

Cited By ~ 31

Author(s):

Cédric Luyet ◽

Peter H. Burri ◽

Johannes C. Schittny

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Programmed Cell Death ◽

Lung Development ◽

Structural Changes ◽

Tissue Transglutaminase ◽

Lung Parenchyma ◽

Lung Maturation ◽

Morphological Criteria ◽

Postnatal Lung Development

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1–0.01 μg/g, days 1–4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19–21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa ( day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.

Download Full-text