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


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.

SUBMITTER: Rinkevich Y 

PROVIDER: S-EPMC4103362 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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

Rinkevich Yuval Y   Montoro Daniel T DT   Muhonen Ethan E   Walmsley Graham G GG   Lo David D   Hasegawa Masakazu M   Januszyk Michael M   Connolly Andrew J AJ   Weissman Irving L IL   Longaker Michael T MT  

Proceedings of the National Academy of Sciences of the United States of America 20140623 27


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 wit  ...[more]

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