UdeM researchers publish on tissue and organ renewal in PLoS ONE

Researchers at the Université de Montréal have identified a cell signaling pathway[1] 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 the TGF-β1 gene 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 with the different role of promoting 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. After amputation or wounding, humans and other mammals form scar tissue and cannot regenerate appendages. Dr. Roy and his team studied the genes in mammalian wound-healing to better understand how the axolotl can perfectly repair its wounds and regenerate its limbs without scaring.

“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 Dr. Roy.

His Université de Montréal research team is one of the few groups worldwide using the axolotl limb as an experimental model to study tissue regeneration. The axolotl limb is used as a case study because researchers can visually determine the stages of its regeneration and it is malleable with three defined axis.

Description of laboratory experimentation

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.

This new Université de Montréal investigation brings fresh insight 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. The study also supports the research efforts on the axolotl in the hope of transposing the regeneration capabilities of the salamander to humans.

[1] Cell signaling pathway:  process by which external factors to cells, such as hormones, send signals to these cells indicating whether they should increase in number, differentiate or commit suicide.

For free access to the article on the PLoS ONE website:

www.plosone.org/doi/pone.0001227

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For more information or a copy of the study please contact:

Sylvain-Jacques Desjardins
International press attaché
Université de Montréal
Téléphone : 514-343-7593
Celular : 514-710-7819
sylvain-jacques.desjardins@umontreal.ca