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Fig. 5 UBIAD1 regulates menaquinone/vitamin K2 metabolism to maintain cranial vasculature. (A,B) Confocal projections of (A) DMSO- and (B) warfarin-treated reh;Tg(gata1:dsRed);Tg(kdrl:GFP) zebrafish reveal that warfarin treatment of zebrafish at 24 hpf leads to cranial hemorrhages (white arrow) by 72 hpf. (C,D) PK (C) and MK-4 (D) treatment at 36 hpf can rescue this warfarin-induced cranial hemorrhaging and vascular defect. (E-H) Confocal projections of PK- and MK-4-treated reh;Tg(gata1:dsRed);Tg(kdrl:GFP) mutant zebrafish showed that (H) MK-4 but not (F) PK treatment at 36 hpf can rescue the reh vascular phenotype by 72 hpf. However, (E) PK and (G) MK-4 treatment had no discernible effect on wild-type zebrafish. Arrows in F indicate cranial hemorrhages. (I) MK-4 or PK treatment rescued the warfarin-induced cranial hemorrhage; however, MK-4 but not PK treatment rescued the reh cranial hemorrhage. (J) The relationship of vitamin K2/MK-4, vitamin K1/PK, UBIAD1 and warfarin.