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Fig. 6. The defect in angiogenesis in Hhex–/– mice includes abnormal VSMC development. Whole-mount {alpha}-SMA immunohistochemistry of E11.5 embryos. (A,D,G) Wild-type embryo. (B,E,H) Hhex–/– embryo with mild phenotype. (C,F,I) Hhex–/– with severe phenotype. In the mildly affected embryos, decreased {alpha}-SMA staining is seen in the cranial vasculature (E) and the dorsal aorta (H). Arrows in (D) and (E) highlight the same vascular branches in both wild-type and Hhex–/– embryos, showing the absence of VSMCs in some vessels. Arrowheads in (G) and (H) indicate the VSMCs in the dorsal aorta. Note the abnormal pattern of {alpha}-SMA staining in the Hhex–/– aorta. In severely affected embryos, there are no VSMCs present in the cranial vessels (F) and a dramatically decreased number are present in the dosal aorta (I), where the pattern of {alpha}-SMA staining is decreased and very irregular.