Patricia E. Phelps
Department of Physiological Sciences
The Phelps laboratory studies the mechanisms of neuronal migration in developing rodent spinal cord. Recent experiments focused on migration errors
in mice with gene deletions in the Reelin-signaling pathway.
Phelps and her colleagues discovered that the loss of Reelin, both Reelin receptors (Apoer2/Vldlr) or the adaptor protein Disabled-1
(Dab1) cause indistinguishable positioning errors in the spinal cord that lead to defects in nociception – a profound reduction in
mechanical sensitivity and an increased sensitivity to noxious heat. Thus the mutants of the Reelin-signaling pathway naturally segregate
the biological basis of thermal and mechanical pain transmission. As there are no apparent differences in the primary afferent nociceptors
or their central terminations, we suspect that positioning errors and dendritic abnormalities in the superficial dorsal horn (laminae I-II)
likely alter pain sensitivity in Reelin-signaling pathway mutants. On-going experiments will characterize the migratory defects and determine
if the hyperalgesia found in Reelin-signaling pathway mutants is caused by Neurokinin-1 receptor-bearing cells that are mispositioned in superficial dorsal horn.
The reeler gene has been conserved in all vertebrate species investigated and has been identified in humans as an autosomal recessive
lissencephaly with cerebellar hypoplasia. Symptoms associated with the human mutation include a severe delay in cognitive development and profound learning disabilities.