Apoptotic cell death in Sp8 deficient brains. TUNEL staining on (a, a', c) E12.5 (coronal) and (b, b', d) E15.5 forebrain sections (sagittal; rostral is to the left). The arrow in (c) demarcates a typical cluster of apoptotic cells, found in cKO, and found from E12.5 to E18.5. Clusters typically contained five to seven apoptotic cells (blow-up in (c)). (d) Tuj/TUNEL double staining in cKO reveals TUNEL+ cells within the putative CP (blue arrow) and presumptive proliferative zones and the IZ (white arrows). (e) Quantification of TUNEL+ nuclei on E10.5, E12.5, E15.5 and E18.5 forebrain sections (n = 3–4 for each stage) shows an increased cell death without Sp8 function. Fate mapping of (f, f') early-born and (g, g') late-born pallial neurons (using BrdU injection at E12.5 or E15.5) on E18.5 sagittal sections. Putative early-born neurons migrate through the CP (f, f'). Their number is diminished in mutant cortices (f') compared to controls (f). In cKO, BrdU+ neurons populate ectopic positions in the upper CP, when compared to the relative position of Tbr1 immunoreactive cells (white arrow in (g')), possibly reflecting the thinned cortex. BrdU labeling at E15.5 appears reduced in the SVZ of mutants (yellow arrow in (g')).