Fig. 3. Gross morphological changes in the forebrains of E12.5 Lifr^-/- embryos relative to control littermates are suggestive of defects related to growth. At rostral regions of the forebrain, the LGE (arrow) in Lifr^-/- embryos (B) was smaller relative to Lifr^+/+/Lifr^+/- (A) littermates. At more caudal regions, decreased thickness of the cerebral wall was observed (arrowhead), as well as decreased size of the LGE and MGE (arrows) in Lifr^-/- (D,F) relative to Lifr^+/+/Lifr^+/- embryos (C,D). At the most caudal regions analyzed (G,H), a reduced caudal ganglionic eminence (arrow) was clearly observed (56% penetrant; Lifr^-/-n=9; Lifr^+/+/Lifr^+/- n=9). Measurements of the area of the LGE revealed a 22% decrease in size in Lifr^-/- embryos (I,J; paired t-test ^**P=0.008; n=5). A concurrent decrease in the mantle zone was also observed, as shown by ß-tubulin III staining (K,L). The number of dying cells in the LGE of Lifr^-/- embryos indicated by TUNEL labeling was normalized to the area of the LGE (M; 0.5±0.1 cells/unit area) and no difference was observed relative to Lifr^+/+/Lifr^+/- embryos (N; 0.5±0.1 cells/unit area; n=4; arrows indicate positive cells; stars indicate examples of autoflorescence). The number of BrdU+ precursors in Lifr^+/+/Lifr^+/- (O; 865±41) was significantly higher than Lifr^-/- embryos (P; 608±15; paired t-test ^**P=0.009; n=5). Scale bar: in A, 100 µm for A-H; in I, 100 µm for I,J; in K, 50 µm for K,L; in M, 50 µm for M-P.