4.6 Article

The global regulatory logic of organ regeneration: circuitry lessons from skin and its appendages

Journal

BIOLOGICAL REVIEWS
Volume 96, Issue 6, Pages 2573-2583

Publisher

WILEY
DOI: 10.1111/brv.12767

Keywords

regeneration; skin; hair follicle; feather follicle; feedback regulation; regulatory circuitry

Categories

Funding

  1. National Natural Science Foundation of China [NSFC 31871468]
  2. Chongqing Talents Program [CQYC2020058022]
  3. Fundamental Research Funds for the Central Universities [2020CDJYGSG003]
  4. Scientific Research Foundation from Chongqing University [02210011044110]
  5. departmental start-up funds, Department of Dermatology, University of Miami
  6. NIHR Manchester Biomedical Research Centre (Inflammatory Hair Diseases Programme)
  7. NIH [R01 GM125322]
  8. [NSFC82003384]

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The regulatory logic in organ regeneration, including quantitative thresholds and qualitative responses, is crucial for understanding the initiation and completion of the process. Examples in skin regeneration highlight the significance of molecular regulatory circuitry, and knowledge of this logic may lead to novel therapeutic strategies.
In organ regeneration, the regulatory logic at a systems level remains largely unclear. For example, what defines the quantitative threshold to initiate regeneration, and when does the regeneration process come to an end? What leads to the qualitatively different responses of regeneration, which restore the original structure, or to repair which only heals a wound? Here we discuss three examples in skin regeneration: epidermal recovery after radiation damage, hair follicle fate choice after chemotherapy damage, and wound-induced feather regeneration. We propose that the molecular regulatory circuitry is of paramount significance in organ regeneration. It is conceivable that defects in these controlling pathways may lead to failed regeneration and/or organ renewal, and understanding the underlying logic could help to identify novel therapeutic strategies.

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