Epidermal Wound Healing in the Nematode Caenorhabditis elegans

Abstract

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.

Specific collagens maintain the cuticle permeability barrier inCaenorhabditis elegans

“…The skin protects the organism from dehydration, from infections and it is thought to act as a physical barrier against environmental toxins. Although the phylum Nematoda diverged from vertebrates very early in evolution, C. elegans skin can also respond to injury by activating wound healing signaling pathways, to hyperosmotic stress by up-regulating glycerol synthesis pathway, and to pathogen invasion by triggering production of antimicrobial peptides, as also seen in vertebrates suggesting conserved function of the skin ( Lamitina et al 2004 ; Pujol et al 2008a , 2008b ; Chisholm 2015 ; Taffoni and Pujol 2015 ).…”

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

“…Mammalian epidermis typically consists of several cell layers, the outermost being an impermeable layer consisting of dead cornified epidermal cells in a sea of extracellular lipids. Despite the differences in epidermal barrier structure in different animals, there are evolutionarily conserved genetic pathways that control the development and regeneration of epidermal barriers in mammals, arthropods, and nematodes (1)(2)(3)(4)(5). Among many examples, the Jun N-terminal kinase (JNK) pathway regulates reepithelialization in diverse animal phyla (6)(7)(8)(9)(10), whereas the Grainy head (Grh) family of transcription factors, under the control of wound-activated receptor tyrosine kinases, activate effector genes that regenerate epidermal barriers in both Drosophila and mammals after wounding (1,(11)(12)(13)(14)(15).…”

Antimicrobial peptides and wound healing: biological and therapeutic considerations

“…Despite differences in morphology and composition of skin layers among different groups of animals, healing of epidermal wounds is a quite conserved process along the evolutionary scale . In Drosophila , epidermal cells under the cuticle of larvae respond to infected wounds by producing the AMP cecropin A .…”

“…In other invertebrates, like the nematode Caenorhabditis elegans , induction of the epidermal AMPs caenacins, upon infection and cuticle damage involves expression of transforming growth factor‐β (TGF‐β) . However, it is not known if wounding elicits neuroimmune or systemic responses as in other organisms . With regard to non‐mammalian vertebrates, a vast literature supports the belief that amphibian skin contains factors associated with high efficiency wound‐healing mechanisms (see section on ) up to regeneration of an entire limb or tail in juvenile animals .…”