The influence of fundamental traits on mechanisms controlling appendage regeneration

Ashley W. Seifert, James R. Monaghan, Matthew D. Smith, Bret Pasch, Adrian C. Stier, François Michonneau, Malcolm Maden

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


One of the most compelling questions in evolutionary biology is why some animals can regenerate injured structures while others cannot. Appendage regeneration appears to be common when viewed across the metazoan phylogeny, yet this ability has been lost in many taxa to varying degrees. Within species, the capacity for regeneration also can vary ontogenetically among individuals. Here we argue that appendage regeneration along the secondary body axis may be constrained by fundamental traits such as body size, aging, life stage, and growth pattern. Studies of the molecular mechanisms affecting regeneration have been conducted primarily with small organisms at early life stages. Such investigations disregard the dramatic shifts in morphology and physiology that organisms undergo as they age, grow, and mature. To help explain interspecific and intraspecific constraints on regeneration, we link particular fundamental traits to specific molecular mechanisms that control regeneration. We present a new synthesis for how these fundamental traits may affect the molecular mechanisms of regeneration at the tissue, cellular, and genomic levels of biological organization. Future studies that explore regeneration in organisms across a broad phylogenetic scale, and within an ontogenetic framework, will help elucidate the proximate mechanisms that modulate regeneration and may reveal new biomedical applications for use in regenerative medicine.

Original languageEnglish (US)
Pages (from-to)330-345
Number of pages16
JournalBiological Reviews
Issue number2
StatePublished - May 2012
Externally publishedYes


  • Appendage
  • Body size
  • Development
  • Fundamental trait
  • Growth
  • Metamorphosis
  • Phylogenetic constraint
  • Regeneration
  • Regenerative medicine

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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