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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.