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Ultrafast distant wound response is essential for whole-body regeneration.

ABSTRACT: Injury induces systemic responses, but their functions remain elusive. Mechanisms that can rapidly synchronize wound responses through long distances are also mostly unknown. Using planarian flatworms capable of whole-body regeneration, we report that injury induces extracellular signal-regulated kinase (Erk) activity waves to travel at a speed 10-100 times faster than those in other multicellular tissues. This ultrafast propagation requires longitudinal body-wall muscles, elongated cells forming dense parallel tracks running the length of the organism. The morphological properties of muscles allow them to act as superhighways for propagating and disseminating wound signals. Inhibiting Erk propagation prevents tissues distant to the wound from responding and blocks regeneration, which can be rescued by a second injury to distal tissues shortly after the first injury. Our findings provide a mechanism for long-range signal propagation in large, complex tissues to coordinate responses across cell types and highlight the function of feedback between spatially separated tissues during whole-body regeneration.

SUBMITTER: Fan Y

PROVIDER: S-EPMC10957142 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Ultrafast distant wound response is essential for whole-body regeneration.

Fan Yuhang Y Chai Chew C Li Pengyang P Zou Xinzhi X Ferrell James E JE Wang Bo B

Cell 20230721 17

Injury induces systemic responses, but their functions remain elusive. Mechanisms that can rapidly synchronize wound responses through long distances are also mostly unknown. Using planarian flatworms capable of whole-body regeneration, we report that injury induces extracellular signal-regulated kinase (Erk) activity waves to travel at a speed 10-100 times faster than those in other multicellular tissues. This ultrafast propagation requires longitudinal body-wall muscles, elongated cells formin ...[more]

PMID: 37480850

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Project description:BackgroundBotryllid ascidians are a group of marine invertebrate chordates that are colonial and grow by repeated rounds of asexual reproduction to form a colony of individual bodies, called zooids, linked by a common vascular network. Two distinct processes are responsible for zooid regeneration. In the first, called blastogenesis, new zooids arise from a region of multipotent epithelium from a pre-existing zooid. In the second, called whole body regeneration (WBR), mobile cells in the vasculature coalesce and are the source of the new zooid. In some botryllid species, blastogenesis and WBR occur concurrently, while in others, blastogenesis is used exclusively for growth, while WBR only occurs following injury or exiting periods of dormancy. In species such as Botrylloides diegensis, injury induced WBR is triggered by the surgical isolation of a small piece of vasculature. However, Botryllus schlosseri has unique requirements that must be met for successful injury induced WBR. Our goal was to understand why there would be different requirements between these two species.ResultsWhile WBR in B. diegensis was robust, we found that in B. schlosseri, new zooid growth following injury is unlikely due to circulatory cells, but instead a result of ectopic development of tissues leftover from the blastogenic process. These tissues could be whole, damaged, or partially resorbed developing zooids, and we defined the minimal amount of vascular biomass to support ectopic regeneration. We did find a common theme between the two species: a competitive process exists which results in only a single zooid reaching maturity following injury. We utilized this phenomenon and found that competition is reversible and mediated by circulating factors and/or cells.ConclusionsWe propose that WBR does not occur in B. schlosseri and that the unique requirements defined in other studies only serve to increase the chances of ectopic development. This is likely a response to injury as we have discovered a vascular-based reversible competitive mechanism which ensures that only a single zooid completes development. This competition has been described in other species, but the unique response of B. schlosseri to injury provides a new model to study resource allocation and competition within an individual.

Project description:The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.

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Ultrafast distant wound response is essential for whole-body regeneration.

Publications

Ultrafast distant wound response is essential for whole-body regeneration.

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