Noncanonical Cell Death in the Nematode Caenorhabditis elegans

Abstract

The nematode Caenorhabditis. elegans has served as a fruitful setting for cell death research for over three decades. A conserved pathway of four genes, egl-1/BH3-only, ced-9/Bcl-2, ced-4/Apaf-1, and ced-3/caspase, coordinates most developmental cell deaths in C. elegans. However, other cell death forms, programmed and pathological, have also been described in this animal. Some of these share morphological and/or molecular similarities with the canonical apoptotic pathway, while others do not. Indeed, recent studies suggest the existence of an entirely novel mode of programmed developmental cell destruction that may also be conserved beyond nematodes. Here we review evidence for these noncanonical pathways. We propose that different cell death modalities can function as backup mechanisms for apoptosis, or as tailor-made programs that allow specific dying cells to be efficiently cleared from the animal.

Microglia Function in Central Nervous System Development and Plasticity

“…However, the investigators also observed in vivo that .60% of Purkinje neurons that were contacted by microglial processes, but not yet phagocytosed, were already expressing molecules associated with damage/PCD (i.e., activated caspase-3). These data suggest a role for microglia in driving the cell death program in neurons that are already rendered vulnerable, a concept that has been suggested in other model organisms (C. elegans and Drosophila) where dying, but not yet dead, cells are engulfed by neighboring cells, including glia (Logan and Freeman 2007;Kinet and Shaham 2014). Similarly, using cultured spinal cord explants from developing rat embryos, microglial ablation, or blocking of microglial-derived TNF-a signaling resulted in a decrease in motoneuron PCD (Sedel et al 2004).…”

Programmed cell death in aging

“…EGL-1 and CED-3 are implicated in promoting mitochondrial fission and causing release of pro-apoptotic factors AIF and EndoG from the mitochondria (Parrish et al, 2001; Wang et al, 2002). Since then additional types of C. elegans developmental cell deaths have been identified (Kinet and Shaham, 2014); for example, cell deaths in the female germ line and during male tale development are EGL-1 independent(Gumienny et al, 1999; Maurer et al, 2007). …”

Molecular Effects of Silver Nanoparticles on Monogenean Parasites: Lessons from Caenorhabditis elegans

“…Parasites exposed to low concentrations of AgNPs also showed up-regulation of pqn-41 (4.15 z-score); this gene is involved in programmed cell death through a non-apoptotic route independent of caspases [ 39 ]. This process has been observed in linker cells during the reproductive development of C. elegans males [ 135 ].…”

“…In vertebrates, this type of non-apoptotic cell death has been observed in the normal development of neurons in the spinal cord and ciliary ganglia [ 136 ]. In addition, patients with neurodegenerative disease associated with polyglutamine like pqn-41 show crenellated nuclei and swollen endoplasmic reticulum and mitochondria in dying neurons [ 39 , 135 ]. Neurodegeneration has been observed in nematodes exposed to nanoparticles [ 135 ]; thus, the expression of pqn-41 in Cichlidogyrus parasites could be related to the damage caused by AgNPs in the nervous system.…”