Wound healing and regeneration: time heals all wounds, but sometimes it needs a little help

Abstract

Molecular Biology of the CellVol. 22, No. 6 ASCB Annual Meeting HighlightsFree AccessWound healing and regeneration: time heals all wounds, but sometimes it needs a little helpWilliam M. Bement, and Phillip A. NewmarkWilliam M. BementDepartment of Zoology, Program in Cellular and Molecular Biology, University of Wisconsin–Madison, Madison, WI 53706Search for more papers by this author, and Phillip A. NewmarkHoward Hughes Medical Institute, Department of Cell and Developmental Biology, University of Illinois at Urbana–Champaign, Urbana, IL 61801Search for more papers by this authorPublished Online:13 Oct 2017https://doi.org/10.1091/mbc.e11-01-0011AboutSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail The Minisymposium on wound healing and regeneration was broad in scope, covering wound repair in organisms ranging from yeast to mammals and across levels of biological organization, ranging from single cells to regeneration of tissues and organs.Bill Bement (University of Wisconsin–Madison) presented results suggesting that the single and multicellular wound responses are linked. Damage to a single cell within a Xenopus epithelium not only elicits calcium elevation and subsequent activation of the small GTPases Rho and Cdc42 around the original wound site, but it also triggers calcium elevation as well as Rho and Cdc42 activation at cell–cell junctions distal to the original wound. At least part of the wound response is mediated via Abr, a dual GEF and GAP for Rho and Cdc42. Abr is apparently responsible for controlling the differential distribution of active Rho and Cdc42 normally seen around single-cell wounds.Keiko Kono (Pellman Laboratory, Dana Farber) described work on development of budding yeast as a model system for single-cell wound repair. Kono has found that laser-induced damage during budding results in rapid redistribution of actin and protein kinase C from the bud site (i.e., the nascent daughter cell) to the site of damage. This actin redistribution is dependent on degradation of the formin, Bni, and represents a polarization switch such that machinery used for daughter cell formation is rapidly shifted toward the wound site.Amber Howard (McNeil Laboratory, Medical College of Georgia) reported on her work investigating the well-known deficit of wound healing caused by diabetes. Although it has long been thought that diabetes suppresses wound repair as a systemic consequence of the disease, Howard found that individual muscle cells from diabetic mice had deficient plasma membrane repair. Further, she demonstrated that simply culturing otherwise normal muscle cells in high glucose resulted in progressive loss of the normal plasma membrane repair response, demonstrating that the response to diabetic conditions is intrinsic to the muscle cells themselves.Michelle Juarez (McGinnis Laboratory, UCSD) described genetic approaches to identify genes coordinating the epidermal response to wounds in the Drosophila embryo. Using wound-dependent fluorescent reporter constructs, Juarez screened panels of deletion mutants to identify genes required for proper activation or inhibition of wound-responsive genes. Juarez identified Flotillin-2 as an inhibitor of wound-responsive genes: Flotillin-2 mutants show broad activation of wound-response genes throughout the embryo, whereas overexpression leads to inhibition of wound-responsive genes. Juarez provided evidence that Src may regulate Flotillin-2 to limit the spread of the epithelial response to wounding.Adrian Halme (University of Virginia) examined how organisms respond systemically to tissue damage. In Drosophila larvae, tissue damage leads to a developmental delay that postpones metamorphosis until the tissue can be repaired. During the course of normal metamorphosis, prothoracicotropic hormone (PTTH) is secreted from neurons that innervate the ring gland; in response to PTTH, the ring gland produces ecdysone, triggering metamorphosis. After tissue damage, PTTH expression is inhibited, resulting in delayed ecdysone production. Halme found that Jun N-terminal kinase (JNK) signaling is required for this damage-induced developmental delay. He also showed that neoplastic tumors produce a similar developmental delay, in which PTTH expression is inhibited by JNK signaling.Phillip Newmark (HHMI/University of Illinois at Urbana–Champaign) discussed intestinal regeneration and differentiation in the planarian. A combination of live imaging and BrdU pulse-chase experiments revealed that intestinal regeneration results from the coordinated differentiation of newly born intestinal cells and remodeling of preexisting intestinal tissue. Newmark described a novel method for purifying intestinal phagocytes, facilitating the identification of intestine-specific monoclonal antibodies and the characterization of intestinal gene expression. The latter results were used to inform a targeted RNAi screen that identified genes required for proper intestinal differentiation and remodeling.FOOTNOTESMolecular Biology of the Cell Volume 22 Page 719MBoC is pleased to publish this summary of the Minisymposium “Wound Healing and Regeneration” held at the American Society for Cell Biology 2010 Annual Meeting, Philadelphia, PA, December 12, 2010.FiguresReferencesRelatedDetails Vol. 22, No. 6 March 15, 2011715-905 Metrics Downloads & Citations Downloads: 64 History Information© 2011 Bement and Newmark. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).PDF download