GoKawiilThese traits make Clytia a unique window into wound healing. The medusae are transparent, allowing researchers to watch cells move in live animals in real time. Their wounds heal rapidly, and unlike mammals there is no immune system to trigger inflammation around a wound or capillary regeneration to obscure the basic mechanics of repair. As a result, scientists can observe epithelial cells stitching damaged tissue back together. Even more importantly, many of the fundamental mechanisms of wound healing appear to be conserved. “A lot of the processes that we see in Clytia’s wound healing are really similar to what you see in all other systems, including mammalian systems,” Malamy explains. In fact, she adds “When you're staring at these epithelial cells, you wouldn't know this was a jellyfish. It could be any kind of squamous epithelial cell sheet, and that's nice, because it means that hopefully what we learn in jellyfish can give us insights into other animals as well.”
Epithelial cells cover all the body’s surfaces. They make up our skin and line the inside of tissues like the gut. Because both the skin and internal epithelial tissues are regularly damaged and must repair themselves, they are a key focus of wound-healing research. Malamy first characterized Clytia epithelial wound healing in 2017 in work initiated with a group of students while she was a Whitman Fellow at the Marine Biological Laboratory (MBL), and she expanded on that work in a paper she co-authored with MBL faculty member Michael Shribak in 2018. Malamy’s new paper in the journal Molecular Biology of the Cell uses Clytia to tackle the confusion in the field over the various mechanisms that have been shown to heal epithelial wounds in different organisms, and wounds of different sizes and shapes. She shows that all epithelial wound healing in Clytia is driven by two key cellular structures that act in sequence to close a wound, and defines a mechanism that explains how these structures are coordinated in all types of wounds.
Confocal microscopy images of tiny wounds within and between Clytia epithelial cells. Actin staining with phalloidin reveals the lamellipodia (green) and Cytoliner (Biotium) stains the membranes (red). Image credit: Jocelyn Malamy
The first structures to form in response to a wound are lamellipodia, which Malamy describes as “foot-like feelers that are actin-rich extensions of the cell.” These feelers act as explorers and have an almost fluid-like motion, similar to amoebas. Lamellipodia extend out of cells at the edge of wounds and crawl across the basement membrane, “a protein sheet that's underneath all epithelial cells in all systems,” she explains. As they “walk”, they drag the cells that produced them forward, eventually stretching the cell body over a wound to close it. Malamy shows in her new paper that these lamellipdodia form even in tiny wounds internal to a single cell, a novel observation.
As the lamellipodia crawl forward, a second wound-healing mechanism comes into play: an actomyosin cable forms at the back of the lamellipodia as they walk forward. As soon as the lamellipodia cover the basement membrane, the cable is triggered to contract.