Figure 7
Defective forward signaling leads to a neuronal migration defect in the hippocampus CA3 region of EphB1/2-deficient mice. (A) H&E staining of coronal hippocampal sections of WT, Ephrin B1 (Efnb1) knockout, EphB1 knockout, EphB2 knockout and compound Ephb1−/−;Ephb2−/− knockout mice, those with a lacZ reporter motif replacing the EphB2 kinase domain (EphB2-lacZ) and those with either a point mutation disrupting EphB2 kinase activity (K661R) or with inactivation of the PDZ domain-binding motif of EphB2 (dVEV994) on an EphB1-deficient background. Scale bar, 500 μm. CA1 and CA3, cornu ammonis subfields 1 and 3 of the hippocampus proper; DG, dentate gyrus. (B) Quantification of the mean cell dispersion (in μm) in the CA1 vs CA3 hippocampal subfield (boxed areas in A; mean ± standard deviation (S.D.), n = 4-8 animals per genotype; *P ≤ 0.01 for Efnb1 knockout mice vs control, **P ≤ 0.001 for compound KO mice vs other genotypes; ANOVA followed by Newman-Keuls multiple comparison test). The compound knockout mice lacking EphB2 or expressing either carboxy-terminally truncated EphB2-lacZ or EphB2 carrying point mutation K661R that inactivates the tyrosine kinase catalytic domain on an EphB1-deficient background display an increased dispersion of the CA3 pyramidal layer that is not seen in the CA1 region. (C) H&E staining of reeler hippocampus showed cellular dispersion in all CA subfields. Specifically, the cellular defects of the medial CA3 region in reeler mice (boxed area) are comparable to those observed in the Ephb1−/−;Ephb2−/− mice.
