Laura Piovani1,2,3, Anna Czarkwiani2,4, Cinzia Ferrario1,5, Michela Sugni6,7,8, Paola Oliveri9,10. 1. Department of Environmental Science and Policy, University of Milan, Via Celoria, 2, 20133, Milan, Italy. 2. Department of Genetics, Evolution and Environment, University College London, London, UK. 3. Center for Life Origins and Evolution, University College London, London, UK. 4. Present Address: DFG-Center for Regenerative Therapies Technische Universität Dresden (CRTD), Dresden, Germany. 5. Center for Complexity and Biosystems, Department of Physics, University of Milan, Via Celoria, 16, 20133, Milan, Italy. 6. Department of Environmental Science and Policy, University of Milan, Via Celoria, 2, 20133, Milan, Italy. michela.sugni@unimi.it. 7. Center for Complexity and Biosystems, Department of Physics, University of Milan, Via Celoria, 16, 20133, Milan, Italy. michela.sugni@unimi.it. 8. GAIA 2050 Center, Department of Environmental Science and Policy, University of Milan, Via Celoria, 2, 20133, Milan, Italy. michela.sugni@unimi.it. 9. Department of Genetics, Evolution and Environment, University College London, London, UK. p.oliveri@ucl.ac.uk. 10. Center for Life Origins and Evolution, University College London, London, UK. p.oliveri@ucl.ac.uk.
Abstract
BACKGROUND: Regeneration is the ability to re-grow body parts or tissues after trauma, and it is widespread across metazoans. Cells involved in regeneration can arise from a pool of undifferentiated proliferative cells or be recruited from pre-existing differentiated tissues. Both mechanisms have been described in different phyla; however, the cellular and molecular mechanisms employed by different animals to restore lost tissues as well as the source of cells involved in regeneration remain largely unknown. Echinoderms are a clade of deuterostome invertebrates that show striking larval and adult regenerative abilities in all extant classes. Here, we use the brittle star Amphiura filiformis to investigate the origin and differentiation of cells involved in skeletal regeneration using a combination of microscopy techniques and molecular markers. RESULTS: Our ultrastructural analyses at different regenerative stages identify a population of morphologically undifferentiated cells which appear in close contact with the proliferating epithelium of the regenerating aboral coelomic cavity. These cells express skeletogenic marker genes, such as the transcription factor alx1 and the differentiation genes c-lectin and msp130L, and display a gradient of morphological differentiation from the aboral coelomic cavity towards the epidermis. Cells closer to the epidermis, which are in contact with developing spicules, have the morphology of mature skeletal cells (sclerocytes), and express several skeletogenic transcription factors and differentiation genes. Moreover, as regeneration progresses, sclerocytes show a different combinatorial expression of genes in various skeletal elements. CONCLUSIONS: We hypothesize that sclerocyte precursors originate from the epithelium of the proliferating aboral coelomic cavity. As these cells migrate towards the epidermis, they differentiate and start secreting spicules. Moreover, our study shows that molecular and cellular processes involved in skeletal regeneration resemble those used during skeletal development, hinting at a possible conservation of developmental programmes during adult regeneration. Finally, we highlight that many genes involved in echinoderm skeletogenesis also play a role in vertebrate skeleton formation, suggesting a possible common origin of the deuterostome endoskeleton pathway.
BACKGROUND: Regeneration is the ability to re-grow body parts or tissues after trauma, and it is widespread across metazoans. Cells involved in regeneration can arise from a pool of undifferentiated proliferative cells or be recruited from pre-existing differentiated tissues. Both mechanisms have been described in different phyla; however, the cellular and molecular mechanisms employed by different animals to restore lost tissues as well as the source of cells involved in regeneration remain largely unknown. Echinoderms are a clade of deuterostome invertebrates that show striking larval and adult regenerative abilities in all extant classes. Here, we use the brittle star Amphiura filiformis to investigate the origin and differentiation of cells involved in skeletal regeneration using a combination of microscopy techniques and molecular markers. RESULTS: Our ultrastructural analyses at different regenerative stages identify a population of morphologically undifferentiated cells which appear in close contact with the proliferating epithelium of the regenerating aboral coelomic cavity. These cells express skeletogenic marker genes, such as the transcription factor alx1 and the differentiation genes c-lectin and msp130L, and display a gradient of morphological differentiation from the aboral coelomic cavity towards the epidermis. Cells closer to the epidermis, which are in contact with developing spicules, have the morphology of mature skeletal cells (sclerocytes), and express several skeletogenic transcription factors and differentiation genes. Moreover, as regeneration progresses, sclerocytes show a different combinatorial expression of genes in various skeletal elements. CONCLUSIONS: We hypothesize that sclerocyte precursors originate from the epithelium of the proliferating aboral coelomic cavity. As these cells migrate towards the epidermis, they differentiate and start secreting spicules. Moreover, our study shows that molecular and cellular processes involved in skeletal regeneration resemble those used during skeletal development, hinting at a possible conservation of developmental programmes during adult regeneration. Finally, we highlight that many genes involved in echinoderm skeletogenesis also play a role in vertebrate skeleton formation, suggesting a possible common origin of the deuterostome endoskeleton pathway.
Authors: Kazuhisa Nakashima; Xin Zhou; Gary Kunkel; Zhaoping Zhang; Jian Min Deng; Richard R Behringer; Benoit de Crombrugghe Journal: Cell Date: 2002-01-11 Impact factor: 41.582
Authors: Silvia Guatelli; Cinzia Ferrario; Francesco Bonasoro; Sandra I Anjo; Bruno Manadas; Maria Daniela Candia Carnevali; Ana Varela Coelho; Michela Sugni Journal: Cell Tissue Res Date: 2022-09-09 Impact factor: 4.051
Authors: Valentina Perricone; Tobias B Grun; Francesco Rendina; Francesco Marmo; Maria Daniela Candia Carnevali; Michal Kowalewski; Angelo Facchini; Mario De Stefano; Luigia Santella; Carla Langella; Alessandra Micheletti Journal: J R Soc Interface Date: 2022-08-10 Impact factor: 4.293