Limb Regeneration In Axolotls

Main Category: Biology / Biochemistry
Article Date: 27 Nov 2007 - 17:00 PDT

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Researchers at the Université de Montréal have identified a cell signaling pathway implicated in limb regeneration in axolotls. The axolotl is a salamander living in Mexican lakes with the unique ability of regenerating damaged or destroyed limbs. Mathieu Lévesque, a PhD student in biochemistry, and supervisor Dr. Stéphane Roy, associate professor at the Faculty of Dentistry, have demonstrated that TGF-β1 is implicated in the preparation phase of axolotl limb regeneration. This gene controls cellular proliferation and migration, which allow the axolotl to regenerate complex structures such as its limbs, tail, jaw, spinal cord and the anterior part of its brain. TGF-β1 is also present in humans, but its role is different: it promotes wound healing and scar formation.

In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Conversely, mammals form scar tissue and cannot regenerate appendages after amputation or wounding. By studying genes involved in mammalian wound healing, Dr. Roy and his team wish to better understand how the axolotl can heal its wounds perfectly and regenerate its limbs without any scarring.

"In the future, understanding the process of tissue regeneration in species such as the axolotl could lead to the development of new treatments in regenerative medicine. People who suffered an amputation, third degree burns, spinal cord injury or who are on the waiting list for an organ could benefit tremendously from these new treatments," explains Stéphane Roy.

Dr. Roy's research team is one of the few groups worldwide using the axolotl limb as an experimental model to study tissue regeneration. The limb is used because of its ease of manipulation, the ability to visually determine the stages of regeneration that have been reached and the fact that it has three defined axis.

The TGF-β1 gene is a member of the transforming growth factor-beta family (TGF-β) and has been identified as a key player in the regulation of wound healing and scar formation in mammals. It is also responsible for limb regeneration in amputated axolotls. Limb regeneration is often considered to be divided into two distinct phases: the preparation phase and the redevelopment phase. Mathieu Lévesque and his research director Stéphane Roy demonstrated that TGF-β1 is up-regulated during the preparation phase of axolotl limb regeneration. This supports the idea that TGF-β1 and TGF-β signaling are implicated in cellular migration and proliferation during the preparation phase.

To verify their hypothesis, the researchers used a pharmacological inhibitor of the TGF-β signaling pathway, SB-431542, to treat regenerating axolotls. Their results show that SB-431542 completely blocked the axolotl's limb regeneration. This clearly demonstrates that TGF-β signaling is essential for limb regeneration in axolotls. In mammals, TGF-β1 is recognized as a pro-fibrosis gene as it promotes rapid closure of the wound, which often results in the formation of a scar.

The results of Mathieu Lévesque and Stéphane Roy, published November 28 in PLoS ONE, bring new insights to the study of tissue regeneration by showing that a signaling pathway leading to scar formation in mammals is essential for axolotl limb regeneration: a process without fibrosis or scaring. This study supports the research efforts on the axolotl in the hope of transposing the regeneration capabilities of the salamander to humans.

Citation: Lévesque M, Gatien S, Finnson K, Desmeules S, Villiard É, et al (2007) Transforming Growth Factor: b Signaling Is Essential for LimbRegeneration in Axolotls. PLoS ONE 2(11): e1227. doi:10.1371/journal.pone.0001227
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