Related Experiment Videos
Abnormal reinnervation of skeletal muscle in a tenascin-C-deficient mouse
C Cifuentes-Diaz1, L Faille, D Goudou
1INSERM, U-488, Le Kremlin, Bicêtre, France. c.diaz@genopole.inserm.fr
Abstract:
The possible involvement of tenascin-C in the reinnervation of a skeletal muscle was investigated in the tenascin-C-deficient mouse (T-/-) produced by Saga et al. (1992; Genes Dev 6:1821-1831). The pattern of reinnervation, observed after denervation of the triangularis sterni muscle, differs in T-/- and wild-type muscles in several traits. Axonal growth and stability of terminal arbors are impaired in the T-/- muscle: Some axons in mutant muscles grow beyond their original targets and reinnervate other synaptic sites, which may become dually innervated. In contrast to wild type, polyinnervation increases with time after denervation in T-/- muscles and is still present 7 months after nerve crush. The expression of a tenascin-C mRNA product disappears between 1 and 2 months after nerve crush. Of interest is that this transcriptional regulation in T-/- muscles occurs when major alterations in the morphology of regenerating endings become obvious. These observations strongly implicate tenascin-C in the formation, maturation, and stabilization of the neuromuscular junction.
Insights
Tenascin-C deficiency impairs skeletal muscle reinnervation, affecting axonal growth and neuromuscular junction stability. Mutant mice show increased polyinnervation, indicating tenascin-C
Area of Science:
- Neuroscience
- Muscle Biology
- Extracellular Matrix Research
Background:
- Tenascin-C is an extracellular matrix glycoprotein implicated in tissue development and repair.
- Neuromuscular junction (NMJ) formation and maintenance are critical for muscle function.
- Understanding the role of specific ECM proteins in reinnervation is crucial for regenerative medicine.
Purpose of the Study:
- To investigate the role of tenascin-C in skeletal muscle reinnervation.
- To characterize the reinnervation patterns in tenascin-C-deficient mice.
- To elucidate the molecular mechanisms underlying tenascin-C's influence on NMJ formation and stability.
Main Methods:
- Utilized tenascin-C-deficient (T-/-) mice and wild-type littermates.
- Induced skeletal muscle denervation in the triangularis sterni muscle.
- Analyzed reinnervation patterns, axonal growth, terminal arbor stability, and polyinnervation over time.
- Assessed tenascin-C mRNA expression post-nerve crush.
Main Results:
- T-/- mice exhibited impaired axonal growth and reduced stability of terminal arbors after denervation.
- Polyinnervation increased significantly and persisted long-term in T-/- muscles compared to wild type.
- Tenascin-C mRNA expression decreased significantly between 1-2 months post-nerve crush, coinciding with morphological changes in regenerating endings.
Conclusions:
- Tenascin-C plays a critical role in the formation, maturation, and stabilization of the neuromuscular junction.
- Deficiency in tenascin-C leads to aberrant reinnervation and impaired NMJ structure.
- These findings highlight tenascin-C as a key regulator of neuromuscular regeneration.