The importance of thrombospondin-1 on limb regeneration of the Ambystoma mexicanum
Saltman, Anna Jesse
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Limb and digit loss poses a significant problem across the animal kingdom. Ambystoma mexicanum, commonly known as the axolotl, however, is one species that has achieved a remarkable ability to bypass the misfortune associated with a lost limb. Viewed as a model organism in regenerative studies, the axolotl retains extraordinary regenerative properties well into adulthood that humans severely lack. While the basics of regeneration have been described, much about the molecular processes of regeneration is still largely unknown. Thrombospondin-1 (TSP-1), an angiogenesis inhibitor, has been identified as a potential factor to play a significant role in the regrowth of limbs. Vascularization of tissues is vital to the survival of biological structures, and TSP-1 has been shown to play a regulatory role in the development and remodeling of tissue vasculature. Here, we study the effect of a loss-of-function mutation in the tsp-1 gene on the process of limb regeneration in the axolotl. Our studies reveal that tsp-1 -/- animals lag in regeneration time, developing smaller blastemas in the first three weeks of regeneration. We show that the loss of TSP-1, however, is not deleterious to the overall process of regeneration as late stage blastemas of the -/- animals catch up in size and development to the wild type animals after three weeks. Our data suggests that while TSP-1 may be important during the initial stages, it may not be required for proper regeneration.