Nerve-Mediated Expression of Histone Deacetylases Regulates Limb Regeneration in Axolotls

This study on axolotls demonstrated that nerve-mediated expression of histone deacetylases, particularly HDAC1, was crucial for limb regeneration. A bi-phasic up-regulation of HDAC1 was observed before the early differentiation stage of regeneration. The use of HDAC inhibitors like MS-275 and TSA delayed limb regeneration by inhibiting local HDAC activities and blastema formation, although they did not affect wound healing. HDAC1 expression was more pronounced in the wound epidermis and was dependent on nerve presence, as denervation prevented HDAC1 elevation and limb regeneration. However, the addition of nerve factors BMP7, FGF2, and FGF8 to denervated limbs restored HDAC1 up-regulation and enhanced limb regeneration, highlighting the essential role of nerve signals in this process.