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@ARTICLE{MeyerZuReckendorf:163734,
      author       = {Meyer Zu Reckendorf, Sofia and Moser, Diana and
                      Blechschmidt, Anna and Joga, Venkata Neeha and Sinske,
                      Daniela and Hegler, Jutta and Deininger, Stefanie and
                      Castanese, Alberto and Vettorazzi, Sabine and Antoniadis,
                      Gregor and Böckers, Tobias and Knöll, Bernd},
      title        = {{M}otoneuron-{S}pecific {PTEN} {D}eletion in {M}ice
                      {I}nduces {N}euronal {H}ypertrophy and {A}lso {R}egeneration
                      after {F}acial {N}erve {I}njury.},
      journal      = {The journal of neuroscience},
      volume       = {42},
      number       = {12},
      issn         = {0270-6474},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DZNE-2022-00473},
      pages        = {2474-2491},
      year         = {2022},
      abstract     = {In postmitotic neurons, several tumor suppressor genes
                      (TSGs), including p53, Rb, and PTEN, modulate the axon
                      regeneration success after injury. Particularly, PTEN
                      inhibition is a key driver of successful CNS axon
                      regeneration after optic nerve or spinal cord injury. In
                      contrast, in peripheral neurons, TSG influence in neuronal
                      morphology, physiology, and pathology has not been
                      investigated to the same depth. In this study, we
                      conditionally deleted PTEN from mouse facial motoneurons
                      (Chat-Cre/PtenloxP/loxP ) and analyzed neuronal responses in
                      vivo with or without peripheral facial nerve injury in male
                      and female mice. In uninjured motoneurons, PTEN loss induced
                      somatic, axonal, and nerve hypertrophy, synaptic terminal
                      enlargement and reduction in physiological whisker movement.
                      Despite these morphologic and physiological changes, PTEN
                      deletion positively regulated facial nerve regeneration and
                      recovery of whisker movement after nerve injury.
                      Regenerating PTEN-deficient motoneurons upregulated P-CREB
                      and a signaling pathway involving P-Akt, P-PRAS40, P-mTOR,
                      and P-4EBP1. In aged mice (12 months), PTEN deletion induced
                      hair loss and facial hyperplasia of the epidermis. This
                      suggests a time window in younger mice with PTEN loss
                      stimulating axon growth after injury, however, at the risk
                      of hyperplasia formation at later time points in the old
                      animal. Overall, our data highlight a dual TSG function with
                      PTEN loss impairing physiological neuron function but
                      furthermore underscoring the positive effects of PTEN
                      ablation in axon regeneration also for the PNS.SIGNIFICANCE
                      STATEMENT Tumor suppressor genes (TSGs) restrict cell
                      proliferation and growth. TSG inhibition, including p53 and
                      PTEN, stimulates axon regeneration after CNS injury. In
                      contrast, in PNS axon regeneration, TSGs have not been
                      analyzed in great depth. Herein we show enhanced peripheral
                      axon regeneration after PTEN deletion from facial
                      motoneurons. This invokes a signaling cascade with novel
                      PTEN partners, including CREB and PRAS40. In adult mice,
                      PTEN loss induces hyperplasia of the skin epidermis,
                      suggesting detrimental consequences when reaching adulthood
                      in contrast to a beneficial TSG role for regeneration in
                      young adult mice. Thus, our data highlight the double-edged
                      sword nature of interfering with TSG function.},
      keywords     = {Animals / Axons: physiology / Facial Nerve Injuries:
                      genetics / Facial Nerve Injuries: pathology / Female /
                      Hyperplasia: pathology / Hypertrophy: pathology / Male /
                      Mice / Motor Neurons: metabolism / Nerve Regeneration:
                      genetics / PTEN Phosphohydrolase: metabolism / Tumor
                      Suppressor Protein p53 / Akt (Other) / CREB (Other) / PTEN
                      (Other) / facial nerve (Other) / motoneuron (Other) / nerve
                      regeneration (Other)},
      cin          = {AG Böckers},
      ddc          = {610},
      cid          = {I:(DE-2719)1910002},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35149515},
      pmc          = {pmc:PMC8944241},
      doi          = {10.1523/JNEUROSCI.1305-21.2022},
      url          = {https://pub.dzne.de/record/163734},
}