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Transient 1a Induction Defines the Wound Epidermis during Zebrafish Fin Regeneration
Unlike mammals, adult teleost fish and urodele amphibians can fully regenerate lost appendages. Understanding what initiates regeneration in these vertebrates is of great interest to the scientific community. It has long been known that the epidermis that forms quickly over an amputated limb stump is critical for initiating regenerative programs. Yet, little of understood of the molecular and cellular mechanisms by which a simple adult epithelium transforms into this key signaling source. Here, we performed a large-scale, unbiased genetic screen for epithelial signaling deficiencies during the regeneration of amputated adult zebrafish fins, from which we identified several new mutants. One gene identified from this screen disrupts a specific component of the extracellular matrix material Laminin, Laminin beta 1a, a factor that we find to be dispensable in uninjured adult animals but required for all stages fin regeneration. Transient induction of this component by amputation polarizes the basal layer of the nascent epithelium, and, in turn, facilitates the synthesis of signaling factors, the positioning of ligand receptors, and the patterning of new bone cells. We also find that normal induction of Laminin beta 1a by injury relies on the function of Fibroblast growth factors, secreted polypeptide signals that are released early upon injury. Our results identify key early steps in the endogenous program for vertebrate appendage regeneration.
Vyšlo v časopise: Transient 1a Induction Defines the Wound Epidermis during Zebrafish Fin Regeneration. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005437
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005437Souhrn
Unlike mammals, adult teleost fish and urodele amphibians can fully regenerate lost appendages. Understanding what initiates regeneration in these vertebrates is of great interest to the scientific community. It has long been known that the epidermis that forms quickly over an amputated limb stump is critical for initiating regenerative programs. Yet, little of understood of the molecular and cellular mechanisms by which a simple adult epithelium transforms into this key signaling source. Here, we performed a large-scale, unbiased genetic screen for epithelial signaling deficiencies during the regeneration of amputated adult zebrafish fins, from which we identified several new mutants. One gene identified from this screen disrupts a specific component of the extracellular matrix material Laminin, Laminin beta 1a, a factor that we find to be dispensable in uninjured adult animals but required for all stages fin regeneration. Transient induction of this component by amputation polarizes the basal layer of the nascent epithelium, and, in turn, facilitates the synthesis of signaling factors, the positioning of ligand receptors, and the patterning of new bone cells. We also find that normal induction of Laminin beta 1a by injury relies on the function of Fibroblast growth factors, secreted polypeptide signals that are released early upon injury. Our results identify key early steps in the endogenous program for vertebrate appendage regeneration.
Zdroje
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