Year: 2021
Type: article
Abstract: Absence of a specialized wound epidermis is hypothesized to block limb regeneration in higher vertebrates. However, the factors preventing its formation in regeneration-incompetent animals are poorly understood. To characterize the endogenous molecular and cellular regulators of specialized wound epidermis formation in Xenopus laevis tadpoles, and the loss of their regeneration competency during development, we used single-cell transcriptomics and ex vivo regenerating limb cultures. Transcriptomic analysis revealed that the specialized wound epidermis is not a novel cell state, but a re-deployment of the apical-ectodermal-ridge (AER) programme underlying limb development. Enrichment of secreted inhibitory factors, including Noggin, a morphogen expressed in developing cartilage/bone progenitor cells, are identified as key inhibitors of AER cell formation in regeneration-incompetent tadpoles. These factors can be overridden by Fgf10, which operates upstream of Noggin and blocks chondrogenesis. These results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates.
Source: Development
DOI: 10.1242/dev.199158
Institutions: University of Cambridge, The Gurdon Institute, University of Aberdeen, Cancer Research UK, Inserm, Institut de Transplantation Urologie en Nephrologie, Center for Research in Transplantation and Translational Immunology, Nantes Université, European Bioinformatics Institute, Wellcome Sanger Institute, Wellcome/MRC Cambridge Stem Cell Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: European Molecular Biology Organization, University of Portsmouth, Wellcome Trust, European Molecular Biology Laboratory, Cancer Research UK, Royal Society, University of Cambridge, Cambridge Trust, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council
Awards: G1524023739, Joint Wellcome and MRC Centre, ‘Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute’, G219317929, Core support for the Wellcome Trust Cancer Research UK Gurdon Institute., Epigenetic Barriers to Cell Fate Reprogramming, Mechanisms for the reprogramming of somatic cell nuclei by eggs and oocytes., Lineage tracing as a strategy to resolve mechanisms of stem cell fate: from development and maintenance to disease and aging., G4810001717, Tracing early mammalian lineage decisions by single cell genomics., G5947339487, G654986153, G660280834, G6806592253, G7505324234, G7579029867, Core support for the Wellcome Trust Cancer Research UK Gurdon Institute., G8961340570
OpenAlex ID: W3162143190