Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration

PNAS, 2014 · DOI: 10.1073/pnas.1410097111 · Published: July 8, 2014

Regenerative Medicine Neurology Genetics

Simple Explanation

This study explores how nerves affect tissue regrowth in mammalian limbs. By studying mice without nerve supply to their hind limbs, researchers examined tissue maintenance, digit tip regeneration, and wound healing. The study found that many tissue processes, like cell turnover and differentiation, can still happen without nerves. However, the absence of nerves leads to defects in bone and nail patterning during digit tip regeneration. These findings are important because they mirror what is seen in humans with spinal cord injuries. This suggests that understanding the role of nerves could lead to better treatments for nerve-related injuries.

Study Duration

3 months

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Cellular turnover, replacement, and differentiation from presumed tissue stem/progenitor cells within hind limb tissues remain largely intact independent of nerve and nerve-derived factors.
2
Regenerated digit tips in the absence of nerves displayed patterning defects in bone and nail matrix.
3
Denervated nail matrixes show increased maximum clone size, fewer nondividing cells, and an overall increase in the number of cells per clone.

Research Summary

The study investigates the role of the peripheral nervous system in tissue replacement in mammalian appendages using clonal analysis of mouse hind limb tissues. The findings indicate that while tissue maintenance and regeneration can occur without nerve supply, nerve-dependent defects arise in bone and nail patterning during digit regeneration. These results have implications for understanding and treating nerve-related pathologies, especially in spinal cord injury patients, by providing insights into nerve and nerve-factor regulation of tissues.

Practical Implications

SCI Skin Complication Treatments

Understanding skin homeostasis mechanisms with and without innervation could identify factors to prevent skin complications in SCI patients.

Bone Repair and Patterning Therapies

Identifying mechanisms through which innervation contributes to bone repair and patterning may help stimulate bone repair in SCI patients.

Clinical Parallels Validation

The mouse model results can be used to validate clinical observations of patterning defects in the ectodermal and mesodermal tissue of SCI patients.

Study Limitations

1
The study primarily uses a mouse model, and findings may not directly translate to humans due to anatomical differences.
2
The study focuses on a 3-month observation period, which may not capture long-term effects of denervation.
3
The skin thickening observations in SCI patients could not be replicated in the mouse model.

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