Migration of sympathetic preganglionic neurons in the spinal cord of a C3G-deficient mouse suggests that C3G acts in the reelin signaling pathway.

Proper positioning of sympathetic preganglionic neurons (SPNs) in the spinal cord is regulated by reelin signaling. SPNs in reeler (which lacks reelin), and in mice deficient in components of the reelin signaling pathway (reelin receptors VldlR and ApoER2, the cytoplasmic adaptor protein Dab1, Src and Fyn of the Src-family of non-receptor protein tyrosine kinases, and CrkL) are located adjacent to the central canal instead of in the intermediolateral column (IML) of the spinal cord. Events downstream of CrkL in control of SPN migration are unclear. The present study asks whether Rap guanine nucleotide exchange factor (GEF) 1 (C3G/Rapgef1), a Ras family GEF that binds CrkL, could act downstream in the reelin signaling pathway in control of SPN migration. SPN migration was examined in a hypopmorphic C3G mutant mouse (C3G(gt/gt)) by using retrograde DiI labeling and NOS immunostaining. The results showed that SPN in the C3G(gt/gt) mutant migrate abnormally toward the central canal as in reeler. However, unlike reeler, levels of reelin in the C3G(gt/gt) spinal cord are normal, and Dab1 immunostaining is undetectable. These results provide genetic evidence that C3G regulates SPN migration, and suggest that C3G acts downstream in the reelin signaling pathway in control of SPN migration. J. Comp. Neurol. 520:3194-3202, 2012. (C) 2012 Wiley Periodicals, Inc.