Digit specific denervation does not inhibit mouse digit tip regeneration

Connor P. Dolan*, Felisha Imholt, Mingquan Yan, Tae Jung Yang, Joshua Gregory, Osama Qureshi, Katherine Zimmel, Kirby M. Sherman, Hannah M. Smith, Alyssa Falck, Eric Leininger, Ling Yu, Regina Brunauer, Larry J. Suva, Dana Gaddy, Lindsay A. Dawson, Ken Muneoka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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. The regenerating mouse digit tip and the human fingertip are mammalian models for epimorphic regeneration, and limb denervation in mice inhibits this response. A complicating issue of limb denervation studies in terrestrial vertebrates is that the experimental models also cause severe paralysis therefore impairing appendage use and diminishing mechanical loading of the denervated tissues. Thus, it is unclear whether the limb denervation impairs regeneration via loss of neurotrophic signaling or loss of mechanical load, or both. Herein, we developed a novel surgical procedure in which individual digits were specifically denervated without impairing ambulation and mechanical loading. We demonstrate that digit specific denervation does not inhibit but attenuates digit tip regeneration, in part due to a delay in wound healing. However, treating denervated digits with a wound dressing that enhances closure results in a partial rescue of the regeneration response. Contrary to the current understanding of mammalian epimorphic regeneration, these studies demonstrate that mouse digit tip regeneration is not peripheral nerve dependent, an observation that should inform continued mammalian regenerative medicine approaches.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalDevelopmental Biology
StatePublished - Jun 2022
Externally publishedYes


  • Blastema
  • Denervation
  • Digit
  • Epimorphic regeneration
  • de novo bone formation


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