Hypoxia-inducible factor 1α in Schwann cells promotes peripheral nerve myelination

Schwann cells are essential for supporting the metabolic activity of neurons and myelination in the peripheral nervous system. While hypoxia is known to influence development in aerobic organisms and has recently been shown to regulate oligodendrocyte differentiation in the central nervous system, its role in Schwann cell function remains less understood. Here we demonstrate that hypoxia-inducible factor 1α (HIF1α) in Schwann cells promotes peripheral nerve myelination. HIF1α protein expression is post-transcriptionally regulated and highly induced in myelinating Schwann cells during development and after injury. We also demonstrated that peripheral nerve tissue experiences hypoxic conditions during physiological development and during regeneration following injury. Stabilization or overexpression of HIF1α in Schwann cells promotes myelination in culture. Analysis of HIF1α targets revealed that HIF1α upregulates genes associated with Schwann cell myelination and repair. Furthermore, conditional deletion of HIF1α in Schwann cells results in delayed morphological and functional recovery from peripheral nerve injury. Together, these findings identify HIF1α as a novel regulator of Schwann cell myelination and nerve repair.