Moreover, E4f1(Nes)KO E18.5 embryos exhibited microcephaly, a developmental defect also observed in some LS patients1 including those harboring the homozygous E4F1A430C mutation which encodes an hypomorpic allele of E4F1, as shown by our complementation assays in E4f1cKO Mouse Embryonic Fibroblasts (MEFs) (Supplementary Figure S1E–G). Here, NES is linked to microcephaly.