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It is unknown whether transient transgenerational epigenetic responses to environmental challenges affect the process of evolution, which typically unfolds over many generations. Here, we show that in C. elegans, inherited small RNAs control genetic variation by regulating the crucial decision of whether to self-fertilize or outcross. We found that under stressful temperatures, younger hermaphrodites secrete a male-attracting pheromone. Attractiveness transmits transgenerationally to unstressed progeny via heritable small RNAs and the Argonaute Heritable RNAi Deficient-1 (HRDE-1). We identified an endogenous small interfering RNA pathway, enriched in endo-siRNAs that target sperm genes, that transgenerationally regulates sexual attraction, male prevalence, and outcrossing rates. Multigenerational mating competition experiments and mathematical simulations revealed that over generations, animals that inherit attractiveness mate more and their alleles spread in the population. We propose that the sperm serves as a "stress-sensor" that, via small RNA inheritance, promotes outcrossing in challenging environments when increasing genetic variation is advantageous., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Caspase proteases execute apoptosis but also function in development. In this issue of Developmental Cell, Weaver et al. report that C. elegans CED-3 caspase promotes animal growth through PMK-1/p38 kinase cleavage, and at the expense of pathogen and stress immunity, revealing an unexpected homeostatic relationship between development and disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Clearance of dying cells is essential for development and homeostasis. Conserved genes mediate apoptotic cell removal, but whether these genes control non-apoptotic cell removal is a major open question. Linker cell-type death (LCD) is a prevalent non-apoptotic developmental cell death process with features conserved from C. elegans to vertebrates. Using microfluidics-based long-term in vivo imaging, we show that unlike apoptotic cells, the C. elegans linker cell, which dies by LCD, is competitively phagocytosed by two neighboring cells, resulting in cell splitting. Subsequent cell elimination does not require apoptotic engulfment genes. Rather, we find that RAB-35 GTPase is a key coordinator of competitive phagocytosis onset and cell degradation. RAB-35 binds CNT-1, an ARF-6 GTPase activating protein, and removes ARF-6, a degradation inhibitor, from phagosome membranes. This facilitates phosphatidylinositol-4,5-bisphosphate removal from phagosome membranes, promoting phagolysosome maturation. Our studies suggest that RAB-35 and ARF-6 drive a conserved program eliminating cells dying by LCD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Long-term studies of Caenorhabditis elegans larval development traditionally require tedious manual observations because larvae must move to develop, and existing immobilization techniques either perturb development or are unsuited for young larvae. Here, we present a simple microfluidic device to simultaneously follow development of ten C. elegans larvae at high spatiotemporal resolution from hatching to adulthood (∼3 days). Animals grown in microchambers are periodically immobilized by compression to allow high-quality imaging of even weak fluorescence signals. Using the device, we obtain cell-cycle statistics for C. elegans vulval development, a paradigm for organogenesis. We combine Nomarski and multichannel fluorescence microscopy to study processes such as cell-fate specification, cell death, and transdifferentiation throughout post-embryonic development. Finally, we generate time-lapse movies of complex neural arborization through automated image registration. Our technique opens the door to quantitative analysis of time-dependent phenomena governing cellular behavior during C. elegans larval development., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nonmotile primary cilia are sensory organelles composed of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis, and signaling protein targeting and localization via as yet poorly understood mechanisms. Here, we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory signaling results in alteration of axoneme length and expansion of a membraneous structure, thereby altering the topological distribution of a subset of ciliary transmembrane signaling molecules. Signaling-regulated alteration of ciliary structures can be bypassed by modulation of intracellular cGMP or calcium levels and requires kinesin-II-driven intraflagellar transport (IFT), as well as BBS- and RAB8-related proteins. Our results suggest that compensatory mechanisms in response to altered levels of sensory activity modulate AWB cilia architecture, revealing remarkable plasticity in the regulation of cilia structure.

Caspase proteases play essential roles in apoptotic cell death, while other proteases are active in necrotic cell death. In a recent paper in Cell, Luke et al. (2007) present findings demonstrating that a gene believed to be a natural protease inhibitor may have a role in preventing necrosis.

Apoptosis, cell death characterized by stereotypical morphological features, requires caspase proteases. Nonapoptotic, caspase-independent cell death pathways have been postulated; however, little is known about their molecular constituents or in vivo functions. Here, we show that death of the Caenorhabditis elegans linker cell during development is independent of the ced-3 caspase and all known cell death genes. The linker cell employs a cell-autonomous death program, and a previously undescribed engulfment program is required for its clearance. Dying linker cells display nonapoptotic features, including nuclear crenellation, absence of chromatin condensation, organelle swelling, and accumulation of cytoplasmic membrane-bound structures. Similar features are seen during developmental death of neurons in the vertebrate spinal cord and ciliary ganglia. Linker cell death is controlled by the microRNA let-7 and Zn-finger protein LIN-29, components of the C. elegans developmental timing pathway. We propose that the program executing linker cell death is conserved and used during vertebrate development.

Engulfment of dying cells plays an important role during animal development and homeostasis, and several proteins involved in this process are known. However, the cell biology underlying phagocyte arm extension and cell corpse degradation is not well understood. A study published in this issue of Developmental Cell (Yu et al., 2006) now demonstrates an important role for the GTPase dynamin in these events.

Sensory organs are often composed of neuronal sensory endings accommodated in a lumen formed by ensheathing epithelia or glia. Here we show that lumen formation in the C. elegans amphid sensory organ requires the gene daf-6. daf-6 encodes a Patched-related protein that localizes to the luminal surfaces of the amphid channel and other C. elegans tubes. While daf-6 mutants display only amphid lumen defects, animals defective for both daf-6 and the Dispatched gene che-14 exhibit defects in all tubular structures that express daf-6. Furthermore, DAF-6 protein is mislocalized, and lumen morphogenesis is abnormal, in mutants with defective sensory neuron endings. We propose that amphid lumen morphogenesis is coordinated by neuron-derived cues and a DAF-6/CHE-14 system that regulates vesicle dynamics during tubulogenesis.