Programmed Cell Death Not as Sledgehammer but as Chisel: Apoptosis in Normal and Abnormal Craniofacial Patterning and Development

Coordination of craniofacial development involves an complex, intricate, genetically controlled and tightly regulated spatiotemporal series of reciprocal inductive and responsive interactions among the embryonic cephalic epithelia (both endodermal and ectodermal) and the cephalic mesenchyme — particularly the cranial neural crest (CNC). The coordinated regulation of these interactions is critical both ontogenetically and evolutionarily, and the clinical importance and mechanistic sensitivity to perturbation of this developmental system is reflected by the fact that one-third of all human congenital malformations affect the head and face. Here, we focus on one element of this elaborate process, apoptotic cell death, and its role in normal and abnormal craniofacial development. We highlight four themes in the temporospatial elaboration of craniofacial apoptosis during development, namely its occurrence at (1) positions of epithelial-epithelial apposition, (2) within intra-epithelial morphogenesis, (3) during epithelial compartmentalization, and (4) with CNC metameric organization. Using the genetic perturbation of Satb2, Pbx1/2, Fgf8, and Foxg1 as exemplars, we examine the role of apoptosis in the elaboration of jaw modules, the evolution and elaboration of the lambdoidal junction, the developmental integration at the mandibular arch hinge, and the control of upper jaw identity, patterning and development. Lastly, we posit that apoptosis uniquely acts during craniofacial development to control patterning cues emanating from core organizing centres.

Download Full-text

Lysosome Biogenesis Mediated by vps-18 Affects Apoptotic Cell Degradation in Caenorhabditis elegans

Molecular Biology of the Cell ◽

10.1091/mbc.e08-04-0441 ◽

2009 ◽

Vol 20 (1) ◽

pp. 21-32 ◽

Cited By ~ 39

Author(s):

Hui Xiao ◽

Didi Chen ◽

Zhou Fang ◽

Jing Xu ◽

Xiaojuan Sun ◽

...

Keyword(s):

Cell Death ◽

Caenorhabditis Elegans ◽

Programmed Cell Death ◽

Direct Evidence ◽

Apoptotic Cell ◽

Apoptotic Cells ◽

Lysosome Biogenesis ◽

Cell Corpse ◽

Lysosomal Protein

Appropriate clearance of apoptotic cells (cell corpses) is an important step of programmed cell death. Although genetic and biochemical studies have identified several genes that regulate the engulfment of cell corpses, how these are degraded after being internalized in engulfing cell remains elusive. Here, we show that VPS-18, the Caenorhabditis elegans homologue of yeast Vps18p, is critical to cell corpse degradation. VPS-18 is expressed and functions in engulfing cells. Deletion of vps-18 leads to significant accumulation of cell corpses that are not degraded properly. Furthermore, vps-18 mutation causes strong defects in the biogenesis of endosomes and lysosomes, thus affecting endosomal/lysosomal protein degradation. Importantly, we demonstrate that phagosomes containing internalized cell corpses are unable to fuse with lysosomes in vps-18 mutants. Our findings thus provide direct evidence for the important role of endosomal/lysosomal degradation in proper clearance of apoptotic cells during programmed cell death.

Download Full-text

The role of caspases as executioners of apoptosis

Biochemical Society Transactions ◽

10.1042/bst20210751 ◽

2021 ◽

Author(s):

Sharad Kumar ◽

Loretta Dorstyn ◽

Yoon Lim

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Evolutionarily Conserved ◽

Aspartyl Proteases

Caspases are a family of cysteine aspartyl proteases mostly involved in the execution of apoptotic cell death and in regulating inflammation. This article focuses primarily on the evolutionarily conserved function of caspases in apoptosis. We summarise which caspases are involved in apoptosis, how they are activated and regulated, and what substrates they target for cleavage to orchestrate programmed cell death by apoptosis.

Download Full-text

Faculty Opinions recommendation of New Arabidopsis thaliana cytochrome c partners: a look into the elusive role of cytochrome c in programmed cell death in plants.

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

10.3410/f.718104360.793488383 ◽

2013 ◽

Author(s):

Daniel Gallie

Keyword(s):

Arabidopsis Thaliana ◽

Cell Death ◽

Cytochrome C ◽

Programmed Cell Death

Download Full-text

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

Current Medicinal Chemistry ◽

10.2174/0929867327666200128105459 ◽

2020 ◽

Vol 27 ◽

Cited By ~ 1

Author(s):

Lifang Zhang ◽

Yu Zhao ◽

Quanmei Tu ◽

Xiangyang Xue ◽

Xueqiong Zhu ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Immune Escape ◽

Hypoxia Inducible Factor ◽

Hpv Infection ◽

Advanced Cervical Cancer ◽

Cervical Carcinogenesis ◽

Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

Download Full-text