The Physiological Components

Image Courtesy of Dr. Steven Scadding, <>

For regeneration to occur, the cells in the limb of a salamander must reenter the cell cycle from a dedifferentiated state. The ability of the cells in the limb to dedifferentiate, form a blastema and become blank slate cells again makes regeneration possible (1). The identity of these blastemal cells has been debated in the literature.

Many molecular signals are involved in the formation of the new limb, most of which scientists still do not completely understand or agree upon. Up until the late bud stage, regeneration is nerve dependent. If the limb is denerved before this stage, regeneration ceases. This is a key difference between development of a limb in an adult and in an embryo, where normal development can happen in the absence of nerves. The later stages of regeneration are nerve independent (8). The purpose for the involvement of the nerves is believed to be for the release of a neurotrophic factor that stimulates the reentry of blastema cells into the cell cycle (17).

Another area of research involves the signals sent from the wound epidermis and the blastema to the dedifferentiated cells. Both retinoic acid and sonic hedgehog protein have been shown to have a role in establishing the pattern formation of the dedifferentiated cells (1, 6, 10). Each has been shown to have the same effect on the patterning in the proximodistal axis in limb buds (10). Another important factor in pattern formation of the regenerating cells is the local interactions and communications between blastemal cells, which can be followed by the introduction of a cell marker to determine the final fate of a cell (1). Also playing a role in regulating the pattern formation are different families of genes (12).



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