Chapter Four - Control of Growth During Regeneration
Section snippets
Cells Participating in Regenerative Growth
A crucial question in epimorphic regeneration is the origin of the cells that participate in regenerative growth. In most cases, robust proliferation is local rather than systemic, and progenitor cells that concentrate around wound sites and are responsible for producing cells needed for regrowth form what is referred to as a blastema. In different systems, blastema cells can come from stem cells residing in injured tissues, differentiated cells that undergo dedifferentiation, or parenchymal
Recognizing Tissue Damage to Initiate Regeneration
When tissues are damaged, the injured cells often undergo apoptosis. Studies in many organisms, including Hydra, Drosophila, and mouse, have established that apoptosis is not only a way to remove damaged cells, but also an important trigger stimulating the proliferation of nearby healthy cells.
After mid-gastric bisection of Hydra, each half regenerates a complete Hydra body. Hydra regeneration is considered to be morphallactic (Park, Ortmeyer, & Blankenbaker, 1970). Nonetheless, proliferation
Regenerative Growth is Controlled by Signaling Networks
After damage is recognized, injury signals need to be translated to proliferating signals to guide the replacement of damaged parts with new tissue. One pathway involved in this link is c-Jun N-terminal kinase (JNK). JNK belongs to the mitogen-activated protein kinase (MAPK) family and is activated by diverse cellular stresses, including wounding, oxidative stress, loss of cell polarity, infection, and apoptosis. It regulates many biological processes including apoptosis, proliferation,
Control of Regenerative Growth by Organ Patterning
The regulation of cell proliferation induced during epimorphic regeneration must be precisely controlled such that neither too little nor too much new tissue is produced. Studies of intercalary regeneration within insect limbs were particularly influential in promoting the hypothesis that growth is influenced by a gradient of positional information (Day and Lawrence, 2000, French et al., 1976, Haynie and Bryant, 1976). According to this hypothesis, during developmental or regenerative growth,
Suppression of Regenerative Growth
As in developmental growth, growth inhibitors also exist in regenerative growth to prevent overgrowth. As regeneration proceeds, the proliferation rate decreases and redifferentiation occurs. This involves the downregulation of progrowth signals and upregulation of antigrowth signals. Growth inhibitors need to be downregulated during the initiation of regeneration, and then activated at the correct time to prevent tissue overgrowth and to allow differentiation to occur. Many studies on
Conclusion
Tissues under homeostasis balance progrowth signals with antigrowth signals. When injury occurs, this balance is rapidly disrupted, and through stress-response mechanisms, the progrowth signals become predominant. The duration and level of elevation of progrowth signals help determine the extent of regenerative growth. In regeneration-competent organs, progrowth signals are prolonged and augmented through collaboration of multiple pathways, including Wnt, BMP, EGFR, JAK-STAT, and Hippo, which
Acknowledgments
Research on regeneration in KDI's lab is supported by Human Frontiers Science Program Grant RGP0016/2010 and the Howard Hughes Medical Institute.
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