Stages in Regeneration
Once a salamander loses a limb, the regrowth process does not happen overnight. It takes approximately 40 days for a limb to fully regenerate (3). While doing so it goes through the following stages:
Image Courtesy of Dr. Susan Byrant, <http://darwin.bio.uci.edu/~mrjc/index.html>
Wound Healing: Epithelial cells rapidly migrate from the circumference of the limb to the plane of amputation. In 12 to 24 hours they form an epidermal covering. This wound epithelium is key to the organization of regenerating cells and the rest of the process can not occur if it does not form properly (1).
Dedifferentiation: Cells undergo a loss of specialization and resemble embryonic mesenchymal cells (12). When they loose their identity it allows for proliferation and repatterning of the cells and ultimatley a new limb.
Budding: The beginning of growth. Dedifferentiated cells accumulate at the end of the stump and form a blastema, the group of cells that will form the new limb. The blastema is the unique cellular structure that initiates growth. This growth zone elongates and forms a cone of cells that eventually forms tissue. The end of this stage is the turning point for nerve dependence. Up until this stage, the regeneration has been nerve dependent (meaning it would be halted if the nerve were damaged).
Pallette: The cone of cells flattens into a paddle shape that will form the digital elements of the new limb.
Differentiation: The reappearance of missing structures and respecialization of cells. The first cells to form are cartilage cells around the end of the amputated bone.
Completion: In about 40 days the entire limb pattern has been regrown. Growth continues and in about 3 months the new limb will be completely indistinguishable from the original limb (2,3).
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