(A) Impaired development of Xrcc4M61R-Nhej1 mice. Actual and expected numbers of Xrcc4M61R-Nhej1 alive pups, E18.5 and E15.5 embryos. (B) Pictures of Xrcc4M61R and Xrcc4M61R-Nhej1 E15.5 embryos. (C) Cleaved-caspase 3 (CC3, red) immunostaining of E15.5 brain slices. Scarce apoptotic cells are detected in the whole dorsal telencephalon from Nhej1-/- and Xrcc4M61R embryos. By contrast, massive neuronal apoptosis is observed in the upper layers of the developing cortex of Xrcc4M61R-Nhej1, Xrcc4-/-, and Nhej1-Paxx DKO embryos. The white boxes indicate the location of the standard window (100 µm wide) spanning from the ventricular to pial surface used to quantify pyknotic nuclei in the dorsal telencephalons (see below). Scale bar: 100 µm. (D) Number of CC3-positive cells in the VZ/SVZ (black)—containing the cycling neural progenitors—and intermediate zone (IZ)/cortical plate (CP) (gray)—containing post-mitotic neurons—of the whole dorsal telencephalons from WT, Nhej1-/-, and Xrcc4M61R embryos. (E) Percentage of apoptotic (pyknotic) nuclei in the ventricular zone (VZ)/sub-ventricular zone (SVZ) (left panel) and the IZ/CP (right panel) found in the standard windows shown in (C). Data were obtained from both hemispheres of three embryos per condition.