Molecular Control of Schwann Cell Development, Plasticity and Tumorigenesis in Peripheral Nerves

Natalie Lai Man Wu, Ph.D.
Cincinnati Children’s Hospital Medical Center

ABSTRACT
In the peripheral nervous system (PNS), Schwann cells are highly versatile glial cells that undertake a broad repertoire of functions, including myelination of axons for saltatory conduction, modulation of synaptic activity at the neuromuscular junction and pain initiation in the dermis. Following nerve injury, quiescent mature Schwann cells exhibit remarkable plasticity by de-differentiating to a pro-repair progenitor-like phenotype to orchestrate nerve regeneration. These highly dynamic processes need to be tightly regulated to prevent pathologies, such as cancer. To date, the molecular mechanisms and signals driving Schwann cell development, myelination and plasticity are not fully understood. In this talk, I will present 1) how Schwann cells in the PNS develop into myelin-forming cells via precise temporal control mediated by the transcriptional factor, Zeb2 and the HIPPO pathway, 2) how these differentiated cells or their progenitors are reprogrammed into tumorigenic cells in nerve cancer via HIPPO pathway dysregulation, and 3) how Schwann cells in nerve tumors demonstrate a tumor cell lineage trajectory during malignant transformation using innovative single-cell genomics. This work advocates an innovative and comprehensive approach to understand the remarkable versatility of Schwann cells in peripheral nerves.

Host: Dr. Alberto Stolfi