Migratory pathway of sympathetic preganglionic neurons in normal and reeler mutant mice

Our previous study showed that the migration of sympathetic preganglionic neurons (SPN) in the spinal cord is affected in the reeler mutant. The present study, using morphometric analysis to describe and compare the location of SPN at progressive developmental stages, provides detailed information on how SPN migrate in the presence or absence of the reelin gene. We found that the initial migration (prior to E11.5) of SPN from the neuroepithelium to the ventrolateral spinal cord is similar in both control (wild-type and heterozygous) and reeler mice. However, as development progressed (E12.5-E15.5), SPN in control mice migrated dorsally toward the intermediate lateral spinal cord region, where 80% settled to form the intermediolateral column (IML); the rest migrated medially to locations between the IML and the central canal. In reeler, 80% of SPN migrated dorsomedially to cluster around the central canal, with the rest distributed between the central canal and the intermediate lateral spinal cord region. The present study also examined the relationship among SPN, Reelin, and radial glial fibers in control and reeler mice. Confocal microscopic studies showed that during their initial migration, SPN in both control and reeler mice were closely apposed to radial glial fibers in the ventrolateral spinal cord. The majority of SPN in control mice then migrated dorsolaterally, in a direction perpendicular to radial glial fibers, to form the IML. In contrast, the majority of SPN in reeler migrated in the same orientation as radial glial fibers back toward the central canal, instead of migrating dorsolaterally to form the IML. A possible explanation for these results is that Reelin acts to prevent SPN from back-migration on radial glial fibers toward the central canal.