title: Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration.
abstract: Mammalian digit regeneration progresses through consistent stages: histolysis, inflammation, epidermal closure, blastema formation, and finally redifferentiation. What we do not yet know is how each stage can affect others. Questions of stage timing, tissue interactions, and microenvironmental states are becoming increasingly important as we look toward solutions for whole limb regeneration. This study focuses on the timing of epidermal closure which, in mammals, is delayed compared to more regenerative animals like the axolotl. We use a standard wound closure device, Dermabond (2-octyl cyanoacrylate), to induce earlier epidermal closure, and we evaluate the effect of fast epidermal closure on histolysis, blastema formation, and redifferentiation. We find that fast epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early epidermal closure eliminates the histolysis stage and results in a regenerate that more closely replicates the amputated structure. We show that tools like Dermabond and oxygen are able to independently influence the various stages of regeneration enabling us to uncouple histolysis, wound closure, and other regenerative events. With this study, we start to understand how each stage of mammalian digit regeneration is controlled.
authors: Division of Developmental Biology, Department of Cell and Molecular Biology Tulane University New Orleans Louisiana 70118 USA; Department of Biology University of Kentucky Lexington Kentucky 40506 USA.
authors: Jennifer
authors: J
authors: Simkin
authors: Division of Developmental Biology, Department of Cell and Molecular Biology Tulane University New Orleans Louisiana 70118 USA.
authors: Mimi C
authors: MC
authors: Sammarco
authors: Division of Developmental Biology, Department of Cell and Molecular Biology Tulane University New Orleans Louisiana 70118 USA; Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station Texas 77843 USA.
authors: Lindsay A
authors: LA
authors: Dawson
authors: Division of Developmental Biology, Department of Cell and Molecular Biology Tulane University New Orleans Louisiana 70118 USA.
authors: Catherine
authors: C
authors: Tucker
authors: Division of Developmental Biology, Department of Cell and Molecular Biology Tulane University New Orleans Louisiana 70118 USA.
authors: Louis J
authors: LJ
authors: Taylor
authors: Department of Medicine Louisiana State University Health Sciences Center New Orleans Louisiana 70112 USA.
authors: Keith
authors: K
authors: Van Meter
authors: Division of Developmental Biology, Department of Cell and Molecular Biology Tulane University New Orleans Louisiana 70118 USA; Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences Texas A&M University College Station Texas 77843 USA.
authors: Ken
authors: K
authors: Muneoka
keywords: Blastema; digit; hypoxia; mouse; regeneration