Schwann cells are the principal glial cells of the Peripheral Nervous System (PNS). These cells originate during embryonic development from the neural crest, a transient population of multipotent cells. Their fundamental role is to act as support cells for peripheral neurons, ensuring their survival, function, and capacity for repair. Schwann cells surround the axons of peripheral nerves, performing structural and metabolic functions necessary for the rapid transmission of electrical signals and the overall health of the nervous system.
Forming the Myelin Sheath
The most recognized function of a Schwann cell is the creation of the myelin sheath, a multilayered lipid and protein covering that insulates axons. A myelinating Schwann cell specifically selects a single, large-diameter axon and begins to wrap its plasma membrane around it in a spiral fashion. This process creates a compact, insulating layer composed of many concentric turns of the cell membrane.
Myelin does not form a continuous sheath but rather is segmented, with small gaps remaining between individual Schwann cells along the axon. These microscopic gaps are known as the Nodes of Ranvier, and they are where the electrical signal is renewed. Instead of traveling slowly down the entire length of the axon, the signal effectively “jumps” from one node to the next, a process called saltatory conduction. This mechanism allows nerve impulses to travel at speeds up to 100 meters per second.
Not all peripheral axons are myelinated; those with smaller diameters are instead associated with non-myelinating Schwann cells, often called Remak cells. In this arrangement, a single Remak Schwann cell can enclose and support multiple small-caliber axons within shallow grooves on its surface. While these axons lack the rapid conduction speed of myelinated fibers, the association still provides structural support and maintenance.
Guiding Nerve Regeneration
A unique and significant capability of Schwann cells is their ability to actively participate in the repair of damaged peripheral nerves, a function largely absent in the Central Nervous System. Following an injury that severs a peripheral axon, the segment disconnected from the cell body rapidly begins to degenerate in a process known as Wallerian degeneration. The Schwann cells in the distal nerve stump, sensing the loss of axonal contact, undergo a dramatic change in their gene expression and morphology.
These cells dedifferentiate from their mature state, shedding their myelin and transforming into a highly plastic, pro-regenerative phenotype. They then proliferate and align themselves within the preserved basement membrane tubes, forming specialized structures called the Bands of Büngner. This structure acts as a natural living scaffold, providing a physical, highly-oriented pathway that guides the regrowing axonal sprouts.
The repair-phenotype Schwann cells secrete a host of guidance molecules and neurotrophic factors into the Bands of Büngner. This combination of a physical scaffold and chemical signals directs the regenerating axon tip, or growth cone, back toward its correct target tissue, such as a muscle or sensory organ.
Supporting Axonal Health
Beyond insulation and acute repair, Schwann cells are engaged in the continuous, long-term metabolic and trophic support of the axons they ensheath. This maintenance function is performed by both myelinating and non-myelinating cells and is necessary for the neuron. Schwann cells constantly supply the axons with metabolic substrates, such as pyruvate and lactate, which are critical energy sources for the neuron’s demanding electrical activity.
These support cells also release a variety of neurotrophic factors that act as molecular sustenance for the neuron. Specific examples include Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Cell Line-Derived Neurotrophic Factor (GDNF). These factors bind to receptors on the axon, promoting neuronal survival, regulating gene expression, and facilitating structural integrity.
Furthermore, Schwann cells play a direct role in maintaining a clean and stable local environment, a state known as homeostasis. In the event of minor damage or routine cellular turnover, Schwann cells actively clear away cellular debris, including fragments of myelin, and help to recruit immune cells like macrophages to assist in the cleanup process. This constant exchange of resources and waste is essential for preventing axonal degeneration and maintaining nerve function throughout life.
When Schwann Cells Fail
When the complex functions of Schwann cells are compromised, it leads directly to a variety of peripheral neuropathies, causing weakness, sensory loss, or pain. These disorders illustrate the dependence of the axon on the structural and metabolic support provided by the surrounding glial cells. A category of diseases known as demyelinating neuropathies results when the myelin sheath produced by the Schwann cell is damaged or improperly formed.
One example is Guillain-Barré Syndrome, an acute autoimmune disorder where the body’s immune system mistakenly attacks the Schwann cells or the myelin they produce. The resulting inflammation and demyelination cause a rapid onset of muscle weakness and paralysis. Another group of conditions, the hereditary Charcot-Marie-Tooth (CMT) diseases, often involve genetic mutations that directly impair the Schwann cell’s ability to create or maintain a healthy myelin sheath.
Specifically, mutations in genes responsible for myelin proteins, such as Peripheral Myelin Protein 22 (PMP22), result in unstable or defective myelin. This structural failure leads to slowed nerve conduction velocities and eventual axonal damage. These diseases reflect the underlying inability of the Schwann cells to perform their fundamental duties of insulation, maintenance, and support.