Schwann Cell - Schwann Cell Lineage

Schwann Cell Lineage

Schwann cells are of neural crest origin. During mouse embryonic development, neural crest cells first differentiate into Schwann cell precursors (SCPs) at around embryonic day (E) 12–13. These precursor cells subsequently differentiate into immature Schwann cells at approximately E15–16, persisting until birth. The postnatal fate of the immature Schwann cell depends on its random association with axons. In a process called radial sorting, whereby Schwann cells segregate axons by extending processes into axon bundles, the Schwann cells that happen to associate with a large diameter axon (>1 μm) will develop into myelinating Schwann cells. Small diameter axons become entrenched in the invaginations of non-myelinating Schwann cells, also called Remak bundles. A key regulator of this process is the axonally-derived signal Neuregulin-1, which binds to cell surface receptors on the Schwann cell and promotes myelination of large diameter axons and sorting of small diameter axons in Remak bundles, dependent on the activity of the β-secretase BACE1 . A further class of non-myelinating Schwann cell, the terminal (or perisynaptic) Schwann cell, exists at the neuromuscular junction, in close proximity to the neuron-muscle synapse. The transition from immature Schwann cell to myelinating/non-myelinating Schwann cell is reversible. When the nerve is injured, Schwann cells can dedifferentiate to form a cell type resembling the immature Schwann cell, often referred to as a denervated or dedifferentiated Schwann cell. This allows them to re-enter the cell cycle in order to proliferate and aid nerve regeneration.