The <i>Caenorhabditis elegans</i> epidermis as a model skin. II: differentiation and physiological roles

Chisholm, Andrew; Xu, Suhong

doi:10.1002/wdev.77

Cited by 98 publications

(89 citation statements)

References 209 publications

(228 reference statements)

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“…Integrity of the cuticle and epidermis might play a more important role in longevity than is generally thought. Deterioration in cuticle structure leads to a loss in barrier function, which may be one of the causes of death of older nematodes (37,40).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas the cuticle of 9-d-old adult nontreated worms started showing signs of agerelated "wrinkling" and disorganization, the cuticle of metformintreated worms resembled that of a young animal. Considering the cuticle's known role in maintaining the shape and size of nematodes (40), it can be assumed that it is this amelioration of cuticle deterioration that allows metformin-treated worms to retain a healthy, young morphology.…”

Section: Metformin-treated Worms Attenuate Age-related Morphologicalmentioning

confidence: 99%

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Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Haes

Frooninckx

Assche

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

305

212

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The antiglycemic drug metformin, widely prescribed as first-line treatment of type II diabetes mellitus, has lifespan-extending properties. Precisely how this is achieved remains unclear. Via a quantitative proteomics approach using the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance. We show that metformin extends lifespan through the process of mitohormesis and propose a signaling cascade in which metformin-induced production of reactive oxygen species increases overall life expectancy. We further address an important issue in aging research, wherein so far, the key molecular link that translates the reactive oxygen species signal into a prolongevity cue remained elusive. We show that this beneficial signal of the mitohormetic pathway is propagated by the peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin signaling might underlie a general principle of prolongevity signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Metformin-treated Worms Attenuate Age-related Morphologicalmentioning

confidence: 99%

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Haes

Frooninckx

Assche

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

305

212

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“…C. elegans molting thus represents a powerful genetic system for studying conserved molecular mechanisms controlling ECM remodeling. The C. elegans molting process has been traditionally separated into two stages termed lethargus (including apolysis and synthesis) and ecdysis (Singh and Sulston 1978;Page and Johnstone 2007;Chisholm and Xu 2012). Initially, the animal gradually decreases physical activity and feeding and becomes lethargic.…”

mentioning

confidence: 99%

“…During apolysis, the larva partially detaches its old cuticle, which then allows for the synthesis of an underlying new cuticle by the epidermis. During ecdysis, a series of stereotypical movements lead to the complete detachment of the old cuticle, followed by the resumption of normal feeding and activities (Singh and Sulston 1978;Page and Johnstone 2007;Chisholm and Xu 2012). The rapid and precise regulation of these steps, which includes the attachment of body wall muscles to the newly synthesized cuticle, is essential to minimize vulnerability and maximize growth potential.…”

mentioning

confidence: 99%

Conserved Ankyrin Repeat Proteins and Their NIMA Kinase Partners Regulate Extracellular Matrix Remodeling and Intracellular Trafficking inCaenorhabditis elegans

Lažetić¹,

Fay

2017

Genetics

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Molting is an essential developmental process in nematodes during which the epidermal apical extracellular matrix, the cuticle, is remodeled to accommodate further growth. Using genetic approaches, we identified a requirement for three conserved ankyrin repeat-rich proteins, MLT-2/ANKS6, MLT-3/ANKS3, and MLT-4/INVS, in Caenorhabditis elegans molting. Loss of mlt function resulted in severe defects in the ability of larvae to shed old cuticle and led to developmental arrest. Genetic analyses demonstrated that MLT proteins functionally cooperate with the conserved NIMA kinase family members NEKL-2/NEK8 and NEKL-3/NEK6/NEK7 to promote cuticle shedding. MLT and NEKL proteins were specifically required within the hyp7 epidermal syncytium, and fluorescently tagged mlt and nekl alleles were expressed in puncta within this tissue. Expression studies further showed that NEKL-2-MLT-2-MLT-4 and NEKL-3-MLT-3 colocalize within largely distinct assemblies of apical foci. MLT-2 and MLT-4 were required for the normal accumulation of NEKL-2 at the hyp7-seam cell boundary, and loss of mlt-2 caused abnormal nuclear accumulation of NEKL-2. Correspondingly, MLT-3, which bound directly to NEKL-3, prevented NEKL-3 nuclear localization, supporting the model that MLT proteins may serve as molecular scaffolds for NEKL kinases. Our studies additionally showed that the NEKL-MLT network regulates early steps in clathrin-mediated endocytosis at the apical surface of hyp7, which may in part account for molting defects observed in nekl and mlt mutants. This study has thus identified a conserved NEKL-MLT protein network that regulates remodeling of the apical extracellular matrix and intracellular trafficking, functions that may be conserved across species.KEYWORDS C. elegans; molting; NIMA kinase; endocytosis; ankyrin repeat proteins M OLTING is a ubiquitous process in nematode species, including Caenorhabditis elegans, and is required for organismal growth and development. Although the observable biomechanics and major morphological features of C. elegans molting were first described nearly 40 years ago (Hirsh et al. 1976;Singh and Sulston 1978), the molecular and cellular mechanisms underlying this complex process are largely unknown. Notably, molting occurs in both pathogenic and nonpathogenic nematode species, and molting factors have been proposed as potential targets for antiparasitic drugs (Page et al. 2014;Gooyit et al. 2015).Mechanistically, molting is the process by which nematodes remodel their epidermal apical extracellular matrix (ECM), termed the cuticle. In C. elegans larvae and adults, the cuticle serves as a mechanical barrier and provides physical and chemical protection from the environment (Page and Johnstone 2007). In addition, similar to the chitin-based exoskeleton of insects and other arthropods, the cuticle is required to facilitate organismal movement in conjunction with attached underlying muscles. Unlike arthropods, however, in nematodes the cuticle is comprised primarily of collagens (Page and Johnstone 20...

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“…1); the biology of the nematode epidermis has recently been reviewed in depth. 17,18 Nematodes lack a rigid exoskeleton; the organismal shape is maintained by internal pressure (the hydrostatic skeleton). The collagenous cuticle is flexible yet contributes to Cross section, highlighting the epidermis and associated extracellular matrices (cuticle and basement membrane).…”

Section: Elegans Epidermal Biologymentioning

confidence: 99%

Epidermal Wound Healing in the Nematode Caenorhabditis elegans

Chisholm

2015

Advances in Wound Care

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Significance: Healing of epidermal wounds is a fundamentally conserved process found in essentially all multicellular organisms. Studies of anatomically simple and genetically tractable model invertebrates can illuminate the roles of key genes and mechanisms in wound healing. Recent Advances: The nematode skin is composed of a simple epithelium, the epidermis (also known as hypodermis), and an associated extracellular cuticle. Nematodes likely have a robust capacity for epidermal repair; yet until recently, relatively few studies have directly analyzed wound healing. Here we review epidermal wound responses and repair in the model nematode Caenorhabditis elegans. Critical Issues: Wounding the epidermis triggers a cutaneous innate immune response and wound closure. The innate immune response involves upregulation of a suite of antimicrobial peptides. Wound closure involves a Ca 2 + -triggered rearrangement of the actin cytoskeleton. These processes appear to be initiated independently, yet, their coordinated activity allows the animal to survive otherwise fatal skin wounds. Future Directions: Unanswered questions include the nature of the damageassociated molecular patterns sensed by the epidermis, the signaling pathways relaying Ca 2 + to the cytoskeleton, and the mechanisms of permeability barrier repair.

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The Caenorhabditis elegans epidermis as a model skin. II: differentiation and physiological roles

Cited by 98 publications

References 209 publications

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Conserved Ankyrin Repeat Proteins and Their NIMA Kinase Partners Regulate Extracellular Matrix Remodeling and Intracellular Trafficking inCaenorhabditis elegans

Epidermal Wound Healing in the Nematode Caenorhabditis elegans

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