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Updated: May 4, 2026
09:46
Analyzing Murine Schwann Cell Development Along Growing Axons
Published on: November 21, 2012
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Jab1 regulates Schwann cell proliferation and axonal sorting through p27
Emanuela Porrello1, Cristina Rivellini, Giorgia Dina
1Institute of Experimental Neurology (INSPE), Division of Neuroscience; 2 Department of Neurology; and 3 Division of Immunology, Transplantation, and Infectious Disease; San Raffaele Scientific Institute, 20132 Milan, Italy.
The Journal of Experimental Medicine
|December 18, 2013
Summary
Jun activation domain-binding protein 1 (Jab1) regulates Schwann cell development for proper axonal sorting. Loss of Jab1 causes neuropathy, but restoring p27 levels rescues this defect, highlighting Jab1
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Axonal sorting is vital for nerve formation, requiring Schwann cell proliferation and differentiation.
- Defects in axonal sorting lead to dysmyelinating peripheral neuropathies.
- Laminin211 and Neuregulin 1 (Nrg1) signals regulate axonal sorting, but their integration in Schwann cells is unclear.
Purpose of the Study:
- To investigate the role of Jun activation domain-binding protein 1 (Jab1) in transducing laminin211 signals within Schwann cells.
- To elucidate how Jab1 regulates Schwann cell number and differentiation during axonal sorting.
- To determine if Jab1 is a key molecule in the pathogenesis of dysmyelinating neuropathies.
Main Methods:
- Inactivation of Jab1 in Schwann cells of mouse models.
- Analysis of Schwann cell proliferation, differentiation, and cell cycle progression.
- Assessment of axonal sorting and myelination.
- Genetic down-regulation of p27 levels in Jab1-null mice.
Main Results:
- Mice lacking Jab1 in Schwann cells exhibited axonal sorting defects and dysmyelinating neuropathy.
- Loss of Jab1 led to increased p27 levels, impairing Schwann cell cycle progression and differentiation.
- Genetic reduction of p27 in Jab1-null mice restored Schwann cell function, axonal sorting, and rescued the neuropathy.
Conclusions:
- Jab1 acts as a crucial mediator of laminin211 signals in Schwann cells, controlling cell cycle, number, and differentiation.
- Jab1 is essential for proper axonal sorting and nerve formation.
- Jab1 dysfunction is implicated in the pathogenesis of dysmyelinating peripheral neuropathies.
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