Reduction of VZ progenitors at the onset of corticogenesis by Lis1–Nde1 double deficiency

() The size of telencephalic vesicles (indicated by dashed blue circles) of the Nde1Lis1 mutant appeared close to normal before E11, but was significantly smaller by E13 compared to that of their littermates. () Correlated with the thinning of cerebral cortex at E12.5, the thickness of cortical VZ and the number of S-phase neural progenitors examined by BrdU transient labeling (in red), was decreased significantly in the Nde1Lis1 mutant. < 0.001. E, Nde1; L, Lis1. Bar: 100 µm. () Reduced neural progenitors in the Nde1Lis1 mutant cortex was indicated by reduced immunostaining of the glutamate transporter GLAST (in red), a marker of radial glial progenitors. Bar: 100 µm. () Substantial cell death was detected in the cerebral cortex of the Nde1Lis1 mutant by TUNEL staining (in green). In contrast, very few TUNEL positive cells were detected in the Nde1 and Nde1Lis1 controls. Bar: 100 µm. () Majority (over 80%) of TUNEL positive cells (in green) in the Nde1Lis1 mutant were newborn post mitotic neurons in the intermediate zone (IZ) and the cortical plate (CP) and expressed DCX (in red). Bar: 100 µm. () Cell-cycle exit profiles of Nde1Lis1progenitors. Pregnant females were given single does of BrdU at E12 and were analyzed 18 h later. Brain sections were stained with antibody to BrdU (in green) and to Ki67 (in red). Cells that exit the cell cycle are counted as those that are positive for BrdU but negative for Ki67, and presented as the percentage of total BrdU positive cells. Approximately 67% of cells labeled by BrdU at E12 became non-progenitor cells in the Nde1Lis1 cortex by E13, while only 25–28% of the Nde1Lis1 or Lis1 progenitors left the cell cycle (<p><b>Copyright information:</b></p><p>Taken from "Lis1–Nde1-dependent neuronal fate control determines cerebral cortical size and lamination"</p><p></p><p>Human Molecular Genetics 2008;17(16):2441-2455.</p><p>Published online 10 May 2008</p><p>PMCID:PMC2486443.</p><p>© 2008 The Author(s).