Study
Nerve dependence in tissue, organ, and appendage regeneration
Kumar, Anoop; Brockes, Jeremy P.
Trends in Neurosciences, 2012
A review of the century-old observation that a denervated appendage does not regenerate, covering the experimental history — denervation, nerve deviation, and identification of nerve-derived factors — across salamanders, mammalian digit tips and other systems.
- Studied in
- Ambystoma mexicanum, Notophthalmus viridescens, Mus musculus, Danio rerio
- Sample size
- review of nerve dependence across regenerating systems
Regeneration of the salamander limb requires nerve supply: a denervated stump forms no blastema and rebuilds nothing, though wound healing proceeds. Deviating a nerve to an abnormal position, combined with a wound, can induce an ectopic blastema and in some protocols a supernumerary limb. Nerve-derived growth factors have been identified, and comparable nerve dependence operates in mammalian digit-tip regeneration.
What it means
The authors' reading, and ours. Where they differ, that difference is the point.
How the authors put it
Nerve dependence is a general feature of appendage regeneration, mediated by diffusible factors from nerves, and is a prerequisite rather than a modulator.
How NatureHQ reads it
The nerve deviation result is the one that changes how you think about this. It is not merely that cutting the nerve stops regeneration; moving a nerve somewhere it does not belong, together with a wound, can start a limb growing there. So the nerve is not permission to proceed with a plan held elsewhere — it is part of what specifies that a limb is what should be built. That is also the honest answer to why this cannot be lifted into human medicine: the requirement is not a molecule to be supplied but a relationship between nerve, wound and positional information that mammals do not maintain.
- A review across systems that differ considerably in mechanism.
- Nerve-derived factors identified so far do not fully account for the requirement.
- Mammalian digit-tip regeneration is far more limited and the comparison is partial.
What this study is used for on NatureHQ
One study can inform several subjects. Here is everywhere this one is cited.
Published by: Cell PressPublished in a Cell Press journal.
doi.org/10.1016/j.tins.2012.08.003
This reference was resolved automatically against Crossref on 2026-08-11.
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