The signal for muscle contraction is transmitted by motoneurons and passed on to skeletal muscles at the neuromuscular junction (NMJ), which as such represents the central node of communication between motor neurons, skeletal muscle, and Schwann cells. Every voluntary movement such as breathing, walking, talking, and eating relies on the appropriate function of the NMJ, therefore much of our behavior, well-being and productivity are governed by this specialized synapse. NMJ dysfunction occurs in a large array of diseases affecting the neuromuscular system including motor neuron diseases such as amyotrophic lateral sclerosis, muscular dystrophies such as Duchenne’s muscular dystrophy, autoimmune diseases such as Myasthenia gravis and congenital myasthenic syndromes. Most of these disorders are currently untreatable and life threatening. Moreover, NMJ maintenance was found to play a key role in weakened muscle function during aging. It is therefore of central importance to understand the mechanisms of NMJ development, maintenance and function under healthy and pathological conditions to develop new therapeutic strategies for patients and an aging society.
The NMJ is a complex structure, formed by a highly organized interplay between motoneuron, muscle endplate and Schwann cells. Its development and functional maturation as well as physiological adaptation throughout life require a coordinated sequence of molecular mechanisms. Our understanding of early NMJ formation was greatly improved by identifying and studying the regulatory proteins agrin, Lrp4, MuSK and Dok-7, which initiate post- as well as pre-synaptic differentiation. While the first steps during post-synaptic differentiation through the agrin-Lrp4-MuSK-Dok-7 signalling axis are well understood, the steps that follow and the mechanisms of retrograde signalling to the nerve are still unresolved. These include cytoskeletal rearrangements, redistribution of proteins, morphological adaptations of the muscle membrane, metabolic alterations and changes in innervation. An even greater lack of knowledge exists about the molecular and cellular processes that are involved during pathological conditions such as motor neuron disease and congenital myasthenic syndromes.
This Research Topic will address recent progress in the field of neuromuscular development and maintenance in health and disease. We will present an overview on molecular and cellular mechanisms guiding NMJ development and maintenance, as well as highlight novel findings related to signalling and cytoskeletal dynamics. Further, we will focus on advances in the understanding and treatment of neuromuscular diseases.
The signal for muscle contraction is transmitted by motoneurons and passed on to skeletal muscles at the neuromuscular junction (NMJ), which as such represents the central node of communication between motor neurons, skeletal muscle, and Schwann cells. Every voluntary movement such as breathing, walking, talking, and eating relies on the appropriate function of the NMJ, therefore much of our behavior, well-being and productivity are governed by this specialized synapse. NMJ dysfunction occurs in a large array of diseases affecting the neuromuscular system including motor neuron diseases such as amyotrophic lateral sclerosis, muscular dystrophies such as Duchenne’s muscular dystrophy, autoimmune diseases such as Myasthenia gravis and congenital myasthenic syndromes. Most of these disorders are currently untreatable and life threatening. Moreover, NMJ maintenance was found to play a key role in weakened muscle function during aging. It is therefore of central importance to understand the mechanisms of NMJ development, maintenance and function under healthy and pathological conditions to develop new therapeutic strategies for patients and an aging society.
The NMJ is a complex structure, formed by a highly organized interplay between motoneuron, muscle endplate and Schwann cells. Its development and functional maturation as well as physiological adaptation throughout life require a coordinated sequence of molecular mechanisms. Our understanding of early NMJ formation was greatly improved by identifying and studying the regulatory proteins agrin, Lrp4, MuSK and Dok-7, which initiate post- as well as pre-synaptic differentiation. While the first steps during post-synaptic differentiation through the agrin-Lrp4-MuSK-Dok-7 signalling axis are well understood, the steps that follow and the mechanisms of retrograde signalling to the nerve are still unresolved. These include cytoskeletal rearrangements, redistribution of proteins, morphological adaptations of the muscle membrane, metabolic alterations and changes in innervation. An even greater lack of knowledge exists about the molecular and cellular processes that are involved during pathological conditions such as motor neuron disease and congenital myasthenic syndromes.
This Research Topic will address recent progress in the field of neuromuscular development and maintenance in health and disease. We will present an overview on molecular and cellular mechanisms guiding NMJ development and maintenance, as well as highlight novel findings related to signalling and cytoskeletal dynamics. Further, we will focus on advances in the understanding and treatment of neuromuscular diseases.