Barrier structures, such as epithelia around tissues or plasma membranes around cells, allow biological systems to maintain a steady molecular composition by preventing random mixing with the environment. In metazoans, injury of epithelial barriers presents a particularly dangerous disturbance of homeostasis, because it allows environmental hazards such as pathogens to enter the organism. In order to avoid extensive infection, a wound has to be rapidly detected and targeted by the organism's anti-microbial defense systems.
Cell biologist Phillipp Niethammer shows how white blood cells can detect a wound site by looking at the translucent tail fins of zebrafish.
In animal tissues, different cell types are able to sense cell and/or barrier damage and participate in protective responses. Among them are white blood cells that rush to injury sites to kill invading pathogens. Amazingly, these cells are able to detect the position of a wound from hundreds of micrometers away within just seconds to minutes after injury. In the thin and translucent tail fins of larval zebrafish this dramatic process can be readily followed by light microscopy (movie 1).
Recruitment of neutrophils (i.e., a special type of white blood cell) to tissue wounds presents one of the first events of a dormant morphogenetic program that ultimately restores barrier function and tissue homeostasis after injury. This program can be conceptualized into two subsequent phases, a short, initial “wound detection” phase followed by a protracted “wound healing” phase.
Cell biologist Phillipp Niethammer uses advanced imaging to investigate processes involved in identifying tissue injury in vertebrates.
“Wound detection” denotes the sum of fast biochemical and physical processes that rapidly carry the information about tissue injury to neighboring or remote cells of the organism. These signals trigger and guide migration of cells towards the wound, and induce secretion of protective and defensive factors. They also initiate a transcriptional cascade that coordinates execution of the subsequent “wound healing” phase, which then leads to tissue repair and regeneration. While the intricate transcriptional regulation of “wound healing” has become a thriving field of biomedical research, the far more rapid, pretranscriptional events of the “wound detection” phase remain surprisingly little studied and understood.
My lab combines advanced imaging approaches and genomic techniques to investigate on a systems level how wounds are detected in vertebrates. Invitral imaging of the wound response in zebrafish larvae has already allowed us to shed light on one previously unrecognized wound detection mechanism, i.e., we identified a novel regulatory role of redox signaling for leukocyte recruitment to injury sites (movie 2). It can be anticipated that invitral imaging will reveal further critical insights into the physiological regulation of injury responses in animals. This should help to more precisely understand both the spatiotemporal mechanisms of tissue damage signaling in healthy organisms as well as during hyper-inflammatory disease and cancer.