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Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9846-51. doi: 10.1073/pnas.1410097111. Epub 2014 Jun 23.

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

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, and Department of Developmental Biology, ryuval@stanford.edu danmontoro@gmail.com irv@stanford.edu longaker@stanford.edu.
2
Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, and ryuval@stanford.edu danmontoro@gmail.com irv@stanford.edu longaker@stanford.edu.
3
Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, and.
4
Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, and Department of Developmental Biology,Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, and.
5
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
6
Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, and Department of Developmental Biology,Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, and ryuval@stanford.edu danmontoro@gmail.com irv@stanford.edu longaker@stanford.edu.

Abstract

The requirement and influence of the peripheral nervous system on tissue replacement in mammalian appendages remain largely undefined. To explore this question, we have performed genetic lineage tracing and clonal analysis of individual cells of mouse hind limb tissues devoid of nerve supply during regeneration of the digit tip, normal maintenance, and cutaneous wound healing. We show that cellular turnover, replacement, and cellular differentiation from presumed tissue stem/progenitor cells within hind limb tissues remain largely intact independent of nerve and nerve-derived factors. However, regenerated digit tips in the absence of nerves displayed patterning defects in bone and nail matrix. These nerve-dependent phenotypes mimic clinical observations of patients with nerve damage resulting from spinal cord injury and are of significant interest for translational medicine aimed at understanding the effects of nerves on etiologies of human injury.

KEYWORDS:

pattern formation; peripheral nerve; stem cell

PMID:
24958860
PMCID:
PMC4103362
DOI:
10.1073/pnas.1410097111
[Indexed for MEDLINE]
Free PMC Article

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