SPP1 and intracranial hemorrhage: Ablation of Itgav, resulting in simultaneous loss of the two integrins αvβ5, a receptor for vitronectin, osteopontin, and Del-1 (developmental locus 1), and αvβ3, a receptor for a variety of ECM proteins, such as fibronectin, vitronectin, laminins, fibrinogen, fibrin, TSP, tenascin-C, vWF, denatured collagen, osteopontin, MMP-2, Del-1, bone sialoprotein, FGF-2, thrombin, and CCN1 (cystein-rich protein 61), leads to 80% embryonic lethality at E9.5, and the other 20% die at P0 with brain hemorrhage [65].