The Role of Genes

The ability to regenerate is characterized by the production of a limb perfectly identical to a newly developed limb. Cells at the amputation plate must be able to utilize positional memory from original development (12). The basic similarities between limb development and limb regeneration suggest that some of the same genes may be expressed in both processes (8). In developing systems, Hox genes (or homeobox-encoding genes) play an important role outgrowth and in determining the position of different cells. Researchers hypothesize that these genes play an equally important role in regeneration (5). Using cDNA isolation, scientists at Harvard Medical School compared the transcriptional patterns in normal and regenerating limbs. Both of the Hox clusters they tested showed increased expression upon amputation (12). Additionally, Hox has been shown to be expressed in the mesenchyme, an indication that cells are specified as early as one to two days post amputation (1). Since then, an several families of homeobox-containing genes have been isolated and extensively documented in the regenerating limb (14).

However, none of the Hox genes are expressed ubiquitously throughout the limb bud in both fore and hind limbs. The same researcher leading the Harvard study published another paper five years later. Still supporting that Hox gene conclusions found before, the researchers aimed to find a candidate for upstream regulators of limb identity. They used a mRNA display and cDNA encoding to identify a family of T-box genes in the newt. Based on the expression patterns, they concluded that limb morphology is strongly influenced by the T-box genes (11). Needless to say, several genetic factors influence limb regeneration patterning, many of which are yet to be found


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