Limb Regeneration In Axolotls

Researchers at the UniversitГ© de MontrГ©al
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
LГ©vesque, a
PhD student in biochemistry, and supervisor Dr. StГ©phane Roy, associate
professor at the Faculty of Dentistry, have demonstrated that TGF-ОІ1 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-ОІ1 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 StГ©phane 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-ОІ1 gene is a member of the transforming growth factor-beta family
(TGF-ОІ) 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 LГ©vesque and his research director StГ©phane
Roy
demonstrated that TGF-ОІ1 is up-regulated during the preparation phase of
axolotl limb regeneration. This supports the idea that TGF-ОІ1 and TGF-ОІ
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-ОІ 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-ОІ signaling is
essential for limb regeneration in axolotls. In mammals, TGF-ОІ1 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 LГ©vesque and StГ©phane 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: LГ©vesque M, Gatien S, Finnson K, Desmeules S, Villiard Г‰, 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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