Figure 9. Cell-Autonomous and Nonautonomous Functions of LIS1 and NDEL1 in Neuronal Migration.

(A) Schematic summary of migration of WT (red) and Ndel1^−/− (green) MADM-labeled cortical projection neurons illustrating the cell-autonomous function of NDEL1 to control invasion into the cortical plate, their target lamina. WT neurons exit the VZ, migrate across the IZ (red arrow), and into the CP along the RGPC fiber, settling within distinct layers of the cortex according to their birth date. Ndel1^−/− neurons migrate out of the VZ and across the IZ (green arrow), but fail to migrate into the CP (−|), representing the target lamina (gray circles) for cortical projection neurons. Ndel1^−/− neurons accumulate below the expanding CP during embryogenesis and eventually remain ectopically located in the white matter (WM) at postnatal stages.

(B and C) Models of cell-autonomous (green) and nonautonomous (blue) in vivo functions of NDEL1 (B) and LIS1 (C) in the developing brain. NDEL1 cell autonomously controls invasion and/or migration within developing target laminae. LIS1 cell autonomously regulates the efficiency of neuronal migration in a dose-dependent manner. In addition, extensive interactions among migrating neurons, either mediated by specific cell-nonautonomous effects of LIS1/NDEL1 or through a general community effect, promote migration of Ndel1^−/− cells before reaching the target laminae and Lis1^−/− cells along the entire path under sparse knockout conditions.