Neuron-specific deletion of the Nf2 tumor suppressor impairs functional nerve regeneration
PLoS ONE. 2016-07-28; 11(7): e0159718
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1. PLoS One. 2016 Jul 28;11(7):e0159718. doi: 10.1371/journal.pone.0159718.
Neuron-Specific Deletion of the Nf2 Tumor Suppressor Impairs Functional Nerve
Schulz A(1), Büttner R(1), Toledo A(2), Baader SL(2), von Maltzahn J(1),
Irintchev A(3), Bauer R(4), Morrison H(1).
(1)Leibniz Institute on Aging, Fritz Lipmann Institute, 07745, Jena, Germany.
(2)Institute of Anatomy, Anatomy and Cell Biology, University of Bonn, 53115,
(3)Department of Otorhinolaryngology, Jena University Hospital, Friedrich
Schiller University Jena, 07747, Jena, Germany.
(4)Institute of Molecular Cell Biology & Center for Sepsis Control and Care
(CSCC), Jena University Hospital, Friedrich Schiller University Jena, 07747,
In contrast to axons of the central nervous system (CNS), axons of the peripheral
nervous system (PNS) show better, but still incomplete and often slow
regeneration following injury. The tumor suppressor protein merlin, mutated in
the hereditary tumor syndrome Neurofibromatosis type 2 (NF2), has recently been
shown to have RhoA regulatory functions in PNS neurons-in addition to its
well-characterized, growth-inhibitory activity in Schwann cells. Here we report
that the conditional knockout of merlin in PNS neurons leads to impaired
functional recovery of mice following sciatic nerve crush injury, in a
gene-dosage dependent manner. Gross anatomical or electrophysiological
alterations of sciatic nerves could not be detected. However, correlating with
attenuated RhoA activation due to merlin deletion, ultrastructural analysis of
nerve samples indicated enhanced sprouting of axons with reduced caliber size and
increased myelination compared to wildtype animals. We conclude that deletion of
the tumor suppressor merlin in the neuronal compartment of peripheral nerves
results in compromised functional regeneration after injury. This mechanism could
explain the clinical observation that NF2 patients suffer from higher incidences
of slowly recovering facial nerve paralysis after vestibular schwannoma surgery.
PMID: 27467574 [Indexed for MEDLINE]