Figure 10.

Zac1 regulates neuronal migration via Pac1 in the developing neocortex. A, Schematic representation of method used to calculate migration index. B–F, E14.5–E18.5 electroporations of pCIG2 (B), pCIG2–Zac1 (C), pCIG2–Pac1 (D), sh-scrambled (E), shZac1 (F), shPac1 (G), pCIG2–Zac1 plus shPac1 (H), and shZac1 plus pCIG2–Pac1 (I). J, Quantitation of migration indices for all electroporations. K, Summary of regulatory interactions between Zac1 and Pac1. Zac1 gain-of-function perturbs radial migration even when Pac1 is knocked down, suggesting that Zac1 controls the expression of other migratory factors. Zac1 knockdown no longer perturbs migration when Pac1 is overexpressed, suggesting that Pac1 is the most critical regulator of migration downstream of Zac1. L, Summary of the role of Zac1 in guiding neuronal migration in the developing neocortex. At the end of glial guided locomotion (steps i–iv), neurons detach from the radial glial scaffold and the leading process extends multiple branches that arborize to the pial surface (step v in pCIG2 control). In neurons in which Zac1 expression is deregulated, branching of the leading process does not occur at the end of terminal translocation (step v; + or − Zac1).