Intriguingly, all PI3K-C2α-inactive embryos that showed improved development resulting from either abrogated extrinsic cell death or TNFR-1 deficiency displayed anophthalmia (lack of one or of both eyes; Fig. 1E), a hallmark feature of perturbed Hedgehog signaling (30). This evidence concerns the gene TNFRSF1A and Anophthalmia.