Supporting Sensory Signals

Science Signaling  17 Feb 2009:
Vol. 2, Issue 58, pp. ec65
DOI: 10.1126/scisignal.258ec65

The development and function of peripheral nerves depends on signaling between axons and Schwann cells, as does regeneration of peripheral nerves after injury. Furusho et al. used transgenic mice to investigate the role of fibroblast growth factor 2 (FGF2) signaling, which plays a critical role in peripheral nerve regeneration, in normal interactions between neurons and Schwann cells. Ultrastructural analysis of the sciatic nerves of mice in which the FGFR1 and FGFR2 receptors had been conditionally deleted from myelinating and nonmyelinating Schwann cells, but not neurons, indicated that myelin and myelinated axons appeared normal. Immunostaining revealed no loss of nonmyelinating Schwann cells. In contrast, C-fibers, small-diameter unmyelinated axons of sensory neurons that carry nociceptive information and are ensheathed by nonmyelinating Schwann cells, showed signs of degeneration. More substantial neuropathy was evident in regions of the dorsal horn of the spinal cord in which C-fibers terminate where sensory information about pain and temperature is integrated. Indeed, behavioral analyses showed that the transgenic mice were slower to withdraw their paws from a hot (55°C) stimulus than were control littermates, although their mechanosensory and motor functions (which involve mostly myelinated axons) were normal. Spinal cord neuropathy became increasingly evident with age; neuropathy was not apparent in 9-day-old mice but was prominent in 1- to 2-month-old mice. Analysis of the time course of spinal cord neuropathy in mice with selective loss of Schwann cell FGFR1 or FGFR2 indicated that signaling from both receptors protected against neuropathy but that FGFR1 played a more substantial role. The authors thus propose that the loss of FGFR1 and FGFR2 signaling in nonmyelinating Schwann cells interferes with their ability to support sensory axons.

M. Furusho, J. L. Dupree, M. Bryant, R. Bansal, Disruption of fibroblast growth factor receptor signaling in nonmyelinating Schwann cells causes sensory axonal neuropathy and impairment of thermal pain sensitivity. J. Neurosci. 29, 1608–1614 (2009). [Abstract] [Full Text]