Attenuation of Mouse Digit Tip Regeneration Following Digit-Specific Denervation

Digit specific denervation does not inhibit mouse digit tip regeneration

It is long-established that innervation-dependent production of neurotrophic factors is required for blastema formation and epimorphic regeneration of appendages in fish and amphibians. In mammals, the regenerating mouse fingertip and the digit tip of a mouse are used as models for epimorphic regrowth. Limb denervation inhibits this response. The fact that limb denervation experiments in terrestrial vertebrates also cause severe paralysis complicates the issue. This causes appendage usage to be impaired and mechanical loading to be reduced. It is not clear whether limb denervation affects regeneration through loss of neurotrophic signals or mechanical load or both. We developed a novel surgery in which we specifically denervated individual digits without affecting ambulation or mechanical loading. We show that digit-specific denervation doesn’t inhibit, but rather attenuates the regeneration of digit tips. This is due in part to a delayed wound healing. Denervated fingers can be treated with a wound dressing to enhance closure. This results in partial recovery of the regeneration response. These studies show that contrary to current mammalian epimorphic regenerative understanding, mouse digit tip regrowth is not dependent on peripheral nerves, a finding that should guide future mammalian cellular regenerative medicine.

Source:
https://www.sciencedirect.com/science/article/abs/pii/S0012160622000501?via=ihub

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