Evidence for a Cell-Specific Action of Reelin in the Spinal Cord

Abstract

Reelin, the extracellular matrix protein missing in reeler mice, plays an important role in neuronal migration in the central nervous system. We examined the migratory pathways of phenotypically identified spinal cord neurons to determine whether their positions were altered in reeler mutants. Interneurons and projection neurons containing choline acetyltransferase and/or NADPH diaphorase were studied in E12.5-E17.5 reeler and wild-type embryos, and their final locations were assessed postnatally. While three groups of dorsal horn interneurons migrated and differentiated normally in reeler mice, the migrations of both sympathetic (SPNs) and parasympathetic preganglionic neurons (PPNs) were aberrant in the mutants. Initially reeler and wild-type SPNs were detected laterally near somatic motor neurons, but by E13.5, many reeler SPNs had mismigrated medially. Postnatally, 79% of wild-type SPNs were found laterally, whereas in reeler, 92% of these neurons were positioned medially. At E13.5, both reeler and wild-type PPNs were found laterally, but by E14.5, reeler PPNs were scattered across the intermediate spinal cord while wild-type neurons correctly maintained their lateral location. By postnatal day 16, 97% of PPNs were positioned laterally in wild-type mice; in contrast, only 62% of PPNs were found laterally in mutant mice. In E12.5-E14.5 wild-type mice, Reelin-secreting cells were localized along the dorsal and medial borders of both groups of preganglionic neurons, but did not form a solid barrier. In contrast, Dab1, the intracellular adaptor protein thought to function in Reelin signaling, was expressed in cells having positions consistent with their identification as SPNs and PPNs. In combination, these findings suggest that, in the absence of Reelin, both groups of autonomic motor neurons migrate medially past their normal locations, while somatic motor neurons and cholinergic interneurons in thoracic and sacral segments are positioned normally. These results suggest that Reelin acts in a cell-specific manner on the migration of cholinergic spinal cord neurons.

Interaction between Dab1 and CrkII is promoted by Reelin signaling

“…Many Reelin-responsive neurons fail to meet this criterion, such as Purkinje cells, and some cortical neurons, which do not migrate far enough when Reelin or downstream components of the pathway are missing. However, the preganglionic autonomic spinal cord neurons (AMNs) appear to migrate beyond their target zones in the absence of Reelin (Phelps et al, 2002;Yip et al, 2000). The migratory pathway of these neurons is complex.…”

Reelin signaling directly affects radial glia morphology and biochemical maturation

“…Indeed, radial glia morphology or Blbp content is normal in the spinal cord of reeler mice (data not shown) as is radial cell migration. Interestingly, only the tangential migration of preganglionic neurons is affected in the spinal cord of reelindeficient mice (Yip et al, 2000;Phelps et al, 2002). Thus, the effect of reelin on tangential cell migration seems to be mediated in a radial glia independent manner, potentially by signaling directly to the migrating neurons.…”

Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

“…Forced limb reduces growth-inhibitory factors and extracellular matrix molecules and regulated growth-promoting factors and cytoskeletal dynamics. There was regulation of adhesion molecules, axonal guidance molecules, and components of synapse formation [e.g., glial cell linederived neurotrophic factor receptor ␣ 1 (Gfra1), brain-derived neurotrophic factor (Bdnf), as well as Neuregulin1 (Nlgn1) and Piccolo (Pcl)] (Garcès et al, 2000;Phelps et al, 2002;Liu et al, 2005;Tao-Cheng, 2006;Fischbach, 2007). Because of the variability in lesion models, training paradigms, investigated time points, or spinal levels, there is no agreement about the importance or specificity of different factors.…”