Fig. 3. Developmental origin of renal agenesis in Npnt-null mice. (A-G) Embryos at the stages indicated, immunostained in wholemount for Calbindin. (A) In the Npnt^+/+ embryo at E11.0 the ureteric bud (arrowhead) has invaded the MM. (B) In the Npnt^-/- embryo the UB (arrowhead) is similar to that in the wild-type embryo. (C) In the Npnt^+/+ embryo at E11.5 the UB has branched (open arrowheads). (D) In the Npnt^-/- embryo the UB (arrowhead) has not extended into the MM (asterisk) or branched. (E) In the Npnt^+/+ embryo at E12.5 the UB has undergone several rounds of branching (arrowheads). (F,G) Npnt^-/- embryos, showing the variable extent of branching at E12.5. (H-J) Transverse sections through E13.5 Npnt^+/+ and Npnt^-/- kidneys. (I,J) Left and right kidneys from one embryo. Note that metanephric fields have been invaded by the UB and nephron development is occurring, but the kidneys are smaller than normal in the Npnt^-/- embryo. Nephrogenesis is occurring, but is less advanced than in the wild-type littermate. (K) Transverse section of an E13.5 Npnt^-/- embryo through the region in which the kidney would normally develop. Note the bilateral kidney agenesis (arrows). (K') Boxed region in K is shown at higher magnification. Broken line demarcates the MM. Scale bars, 100 µm. Go, gonad; In, intestine; MM, metanephric mesenchyme; UB, ureteric bud.