How do interactions between the wound epidermis influence regeneration Essay

Wound healing (18), ion flux (20), and interactions between the wound epidermis and the underlying tissue appear critical for regenerative outgrowth. Recent work suggests that programmed cell death may play a role in triggering regenerative responses in many different organisms.(21) Apoptotic cells have been observed during early phases of regeneration in several animals that can regenerate missing tissues planarians, Xenopus, and newts.(22-26) Apoptotic cells have been shown to provide a number of signals that can regulate wound healing and regeneration. MAPK signaling through Jun kinase is important both for initiating apoptosis and production of Wnt (Wg) and BMP (Dpp) mitogens.(27-29) The extent to which these factors are required for stimulating compensatory proliferation remains unclear.
Injury-induced apoptotic signals are also required to maintain tissue homeostasis. When cells of the adult Drosophila midgut are injured by toxins or induced to undergo apoptosis, intestinal enterocytes secrete the cytokine Unpaired, which stimulates proliferation of intestinal stem cells through activation of the Jak/Stat pathway.(30) Similarly, in the mouse intestine massive induction of apoptosis (via intestine-specific knockout of the p53 inhibitor Mdm2) is eventually compensated in adults by increased proliferation and expansion of the stem cell pool.(31) Apoptotic cells also contribute to homeostasis in epithelia by lipid-based signaling (sphingosine-1-phosphate) that triggers actomyosin contraction in the surrounding cells, leading to the extrusion of the dying cells.(32) These observations suggest many potential roles for dead and dying cells to alter cell behavior at sites of injury.
New cells can be generated in a variety of ways, including proliferation of a resident stem cell population, division of terminally differentiated cells, or dedifferentiation/transdifferentiation of mature cells to a stem cell-like precursor or another cell type. The extent to which each mode is used varies between species and even across tissues within the same species.(19) The source of regenerative cells in vertebrates varies between tissues and organisms, and in some cases remains a matter of continued debate. Many vertebrate tissues contain adult stem cells that play important roles in tissue turnover and homeostasis. Nonetheless, division, dedifferentiation, and transdifferentiation of differentiated cells contribute to regeneration in several different contexts. For example, whereas liver progenitor cells appear to be major sources of new hepatocytes under conditions of extreme damage or chronic disease, restoration of liver mass after partial hepatectomy or mild liver injury is largely accomplished through proliferation of remaining hepatocytes.(33) Similarly, recent lineage-tracing experiments indicate that after damage to the zebrafish heart, existing cardiomyocytes undergo dedifferentiation and proliferate to generate new cardiomyocytes for replacing lost heart mass.(34,35)
Investigations of model organisms have begun to characterize the cellular sources of regeneration, define their potency, and identify molecules required for restorative events. Thus, there is now a great opportunity for cell biological studies to link gene function to cellular behavior. One of the long-term goals of regeneration research is to understand why humans have such limited regenerative potential and what, if anything, can be done to improve it. The knowledge gained from studying cell biological questions in model organisms should help drive such future efforts of regenerative medicine.