Developmentally regulated impediments to skin reinnervation by injured peripheral sensory axon terminals.
The structural plasticity of neurites in the central nervous system (CNS) diminishes dramatically after initial development, but the peripheral nervous system (PNS) retains substantial plasticity into adulthood. Nevertheless, functional reinnervation by injured peripheral sensory neurons is often incomplete [1-6]. To investigate the developmental control of skin reinnervation, we imaged the regeneration of trigeminal sensory axon terminals in live zebrafish larvae following laser axotomy. When axons were injured during early stages of outgrowth, regenerating and uninjured axons grew into denervated skin and competed with one another for territory. At later stages, after the establishment of peripheral arbor territories, the ability of uninjured neighbors to sprout diminished severely, and although injured axons reinitiated growth, they were repelled by denervated skin. Regenerating axons were repelled specifically by their former territories, suggesting that local inhibitory factors persist in these regions. Antagonizing the function of several members of the Nogo receptor (NgR)/RhoA pathway improved the capacity of injured axons to grow into denervated skin. Thus, as in the CNS, impediments to reinnervation in the PNS arise after initial establishment of axon arbor structure.
O'Brien
Georgeann S
GS
Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
Martin
Seanna M
SM
Söllner
Christian
C
Wright
Gavin J
GJ
Becker
Catherina G
CG
Portera-Cailliau
Carlos
C
Sagasti
Alvaro
A
D000818:Animals; D019771:Axotomy; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000502:physiology*; D012867:Skin / Q000294:innervation*; D014276:Trigeminal Nerve / Q000166:cytology*; D061221:Trigeminal Nerve Injuries; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D017931:DNA Primers; D018076:DNA, Complementary; C541256:Nogo receptor, zebrafish; D011956:Receptors, Cell Surface; D029961:Zebrafish Proteins; D020742:rhoA GTP-Binding Protein