Fig. 5
Neural precursor cell migration is compromised when CBP is knocked out at an early time-point in vivo. a1,2 BrdU/EdU fate mapping experimental design. For analysis of embryonic development, BrdU was injected at E14.5 labeling proliferating and then migrating cells within the ventricular zone. At E16.5, animals were sacrificed after EdU administration for marking currently proliferating cells. For analysis of postnatal migration from the V-SVZ towards the corpus callosum and OB through the RMS, BrdU was administered at P15 and EdU at P30. b1,3 BrdU fate-mapping in frontal sections from the ventricular zone towards the outer neocortical layers, which are marked with circles at E16.5. b2,4 BrdU fate-mapping in frontal sections at E16.5 displaying the developing hippocampus with 1ry, 2ry and 3ry matrix. b5 Percentage of migrating BrdU+ cells that reached the circled outer layers of the neocortex. In mutant animals, significantly less cells reached their destination. b6 Percentage of migrating BrdU+ cells that reached the 3ry matrix compared to all BrdU+ cells, with a significantly smaller proportion of BrdU+ cells reaching the 3ry matrix after loss of CBP. c1,3 Frontal sections through V-SVZ at P30 with arrows showing BrdU+ cells within the V-SVZ of control animals and within the cell accumulation seen in hGFAP-cre::CBPFl/Fl mice. c2,4 Frontal sections through the OB at P30, showing BrdU+ cells after their migration through the RMS (arrows). c5 The BrdU+ rate was found to be significantly higher within the cell accumulation than in the V-SVZ of control animals and significantly lower in the GCL of the OB of transgenic animals. d1,2 BrdU staining of the CC genu and V-SVZ/RMS in sagittal sections at P30 after BrdU injection at P15. Migrated BrdU+ cells in the CC are labelled with arrows. d3 BrdU+ rate in the corpus callosum at P30, significantly lower in hGFAP-cre::CBPFl/Fl mice. Scale bar: 50 μm (b1–4), 30 μm (c1–4); 100 μm (d1,2); *p < 0.05, **p < 0.01