Research

During her postdoctoral work in Dr. Brad Zuchero’s lab at Stanford University, Dr. Kantarci studied the development of excitability in dorsal root ganglion (DRG) somatosensory neurons that innervate peripheral targets such as hair and skin to transmit sensory input.  Isolating DRG neurons away from Schwann cells that myelinate or ensheathe DRG axons during development inhibited their excitability, rendering them hypoexcitable and unable to propagate action potential trains (Fig.1A). With Dr. Du Bois’s lab at Stanford, the excitability-inducing molecule secreted by Schwann cells was identified as Prostaglandin E₂ (PGE₂). Schwann cell-secreted PGE₂ increased the expression of voltage-gated sodium channels and other genes important for neural development in sensory neurons and restored excitability in cultured DRG neurons (Fig.1B). Schwann cells express only one of the PGE₂ synthases (Fig.1C), Ptges3. Dr. Kantarci and colleagues generated a transgenic mouse line with floxed alleles of Ptges3 to block PGE₂ synthesis in Schwann cells (Ptges3-Flox mice). Blocking PGE₂ synthesis in Schwann cells (Ptges3-cKO) led to profound developmental defects in sensory behavior, including proprioception, thermoception and nociception⁷ (Fig. 1D–F). Overall, this previous study demonstrated an essential role for peripheral glia in inducing neural excitability during development and uncovered PGE₂ as a key molecule secreted from glia in this process cells (Kantarci, Elvira et al., Cell, 2024).