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. Author manuscript; available in PMC: 2010 Apr 16.
Published in final edited form as: Cell. 2009 Oct 16;139(2):285–298. doi: 10.1016/j.cell.2009.07.047

Figure 5.

Figure 5

Ubiquitous production of Norrin during embryogenesis leads to vascular disorganization

(A) Targeted insertion of a Cre-activated Norrin expression cassette upstream of the Ubb gene. Cre-mediated recombination eliminates a loxP-flanked beta-geo and three transcription termination sites, permitting transcription of Norrin-IRES-EGFP.

(B) Upper panel, Z/Norrin;Sox2-Cre embryos have a severe defect in yolk sac vascular development and retarded embryonic growth at E10.5. Lower panels, anti-PECAM immunostaining at E10.5 shows generalized vascular disorganization in a Z/Norrin;Sox2-Cre embryo (right).

(C) Flat-mounted E10.5 yolk sacs show an orderly hierarchy of vessel sizes in WT (left), and undeveloped and disorganized vasculature in a Z/Norrin;Sox2-Cre yolk sac (right). Scale bar, 200 um.

(D) Dorsal aorta at E9.5. vSMCs are absent in the Z/Norrin;Sox2-Cre aorta. Scale bar, 50 um.

(E–I) Lethality caused by ubiquitous Norrin production is suppressed in a Fz4−/− background (E), and partially suppressed in Fz4+/− and Lrp5−/−backgrounds (F–I).