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

Abstract

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.

Interaction between Dab1 and CrkII is promoted by Reelin signaling

“…They first migrate out from the ventricular zone, then dorsally in the spinal cord. In the absence of Reelin, most of the AMNs then migrate medially inward along radial glia, whereas in the presence of Reelin most of these neurons remain in the lateral spinal cord (Yip et al, 2003). Thus, the late-phase medial migration of the AMNs observed in the Reeler mutants could conceptually be prevented by Reelin-induced Dab1-CrkII complexes.…”

Spinal Motor Neuron Migration and the Significance of Topographic Organization in the Nervous System

“…1 . Reelin is also expressed in the spinal cord and is required for the normal migration of PG neurons as well as the layering of the dorsal horn laminae (Yip et al 2000(Yip et al , 2003a(Yip et al , 2004(Yip et al , 2009Villeda et al 2006 ;Phelps et al 2002 ). Interestingly, the altered position of PG motor neurons in Reeler mutants appears to have no bearing on their connectivity to their ganglionic targets (Yip et al 2003b ) arguing that cell body position and axon projections of motor neurons can be uncoupled.…”

Lis1 reduction causes tangential migratory errors in mouse spinal cord

“…SPNs and PPNs are among the earliest born neurons in the rodent spinal cord (Nornes and Carry, 1978; Barber et al, 1991; Yip et al, 2004b) and complete their rather complex migration early during spinal cord development (Phelps et al, 1991, 2002; Yip et al, 2000, 2003a). To determine whether ectopic preganglionic neurons detected in P0 Lis1 +/− spinal cord would eventually migrate into the intermediate horn, we evaluated their positions 1 month later.…”

“…Errors in preganglionic neuron migration were reported in the spinal cords of cdk5 (Yip et al, 2007) and reeler mutants (Yip et al, 2000, 2003a; Phelps et al, 2002; Kubasak et al, 2004). Consistent with our results in the Lis1 +/− spinal cord, the primary radial migration of cdk5 and reeler SPNs and PPNs from the ventricular zone to the ventrolateral spinal cord appears unaffected.…”

“…In cdk5 −/− mice, all SPNs and PPNs are arrested in the ventral spinal cord adjacent to the SMNs (Yip et al, 2007), whereas only a portion of these cells do not reach their correct locations in Lis1 +/− mice. In rl −/− mice, all SPNs and PPNs complete their tangential migration dorsally, but then do not stop in the IML and instead migrate toward the ventricular zone (Yip et al, 2000, 2003a; Phelps et al, 2002), probably along radial glia (Phelps et al, 1993). An unusual migratory error found in both rl −/− and Lis1 +/− mice involves SPNs migrating out the ventral roots and into the dorsal root ganglia during embryonic development (Han et al, 2008).…”