Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes
Figure 7
Synergistic interaction of Nde1 with Dag1.
(A) Histological analysis of Nde1, Dag1 double mutants. Brain sections of 4-mo-old adult mice were stained with Cresyl violet to view cortical neuronal lamination of indicted mutants. More than 4 litters were analyzed; the Nde1 Dag1 double deficient brains showed significantly more severe disorganization of cortical neurons; the penetrance of synergistic enhancement of Nde1 and Dag1 signal mutant phenotypes by the double mutant was found to be 100%; representative pictures of spatially matched cortical sections of one set of the littermates were shown. Bars: 100 µm. (B) Immunohistological analysis of cortical superficial layer II/III neurons with the Cux1 antibody (red) on early postnatal (P3.5) spatially matched coronal brain sections of indicated genotype. Six litters were analyzed; the synthetic neuronal migration defect of Nde1 and Dag1 double mutations was found with a 100% penetrance; representative pictures of spatially matched cortical sections of one set of the littermates were shown. Bar: 100 µm. (C) Immunohistological analysis of cortical deep layer V/VI neurons with the FoxP2 antibody (red) on early postnatal (P3.5) spatially matched coronal brain sections of indicated genotype. Six litters were analyzed; representative pictures of spatially matched cortical sections of one set of the littermates were shown. Bar: 100 µm. (D) Cortical distribution of Cux1+ and Foxp1+ neurons of indicated mutants. The neocortex of each cortical section was divided equally into 10 layers between the lateral ventricle and the pial surface. Layer 1 is next to the ventricle and layer 10 is immediately beneath the pial surface. About 1,000 Cux1+ neurons or Foxp2+ neurons from 4–5 sets of littermates were analyzed. The fractions (%) of Cux1+ or Foxp2+ neurons in each layer were plotted to indicate the relative distance of neuronal migration from the ventricular surface. (E) Immunohistological analysis of ectopically over-migrated neurons in the MZ. Mature cortical neurons were immunostained by NeuN antibody (red). The cortical pial surface was highlighted by Nidogen immunoreactivity (green) and all sections were stained with Hoechst to view general cell distribution. Bar: 100 µm.