Download Inhibition of Regenerative Responses in the Salamander

Inhibition of Regenerative Responses in the Salamander Limb by Extracellular Matrix
Cynthia Shu
Mentor: David M. Gardiner
The purpose of this study was to characterize of the role of position-specific extracellular matrix
(ECM) in regenerative responses of the salamander limb. The ability of salamanders to regenerate
limbs is a riveting process that is under intense study, with the general goal of inducing regeneration
in humans. Previous studies have characterized the process, but the complete mechanism has yet to
be unraveled. The same genes expressed during limb development have been identified in
regenerating limbs, indicating the re-expression of developmental genes during regeneration. It has
been speculated that the adult human’s inability to regenerate is due to inhibition of developmental
genes, which are present but inactive. Studies on chick embryos have found that the ECM is an
influential factor in limb development. The ECM contains growth factor-binding molecules such as
heparan sulfates (HS), which possess the ability to bind signaling molecules to either inhibit or
activate a cellular response. In this study, the influence of amputation plane derived-ECM was
investigated using a surgically inducible model of regeneration. Results indicate that anterior/noncontralateral grafts into anterior host sites inhibit a regenerative response, and posterior grafts lead to
a normal induced regenerative response. We propose that the HS in posterior ECM grafts are
occupied by growth factors and, thus, cannot bind activating signals released by the nerve, leading to
a host growth response. In contrast, the HS of anterior ECM are unbound by growth factors and can
therefore bind the activating signals, inhibiting a regenerative response.