Figure 4. Draxin expression in the neocortex is critical for corticofugal and thalamocortical development.

(a) Schematic of the Z/draxin transgene. Specific expression of draxin in the neocortex of draxin^−/− mice (Emx1^Cre/+;Z/draxin hetero;draxin^−/−) is achieved by crossing Z/draxin homo;draxin^−/− mice with Emx1^Cre/+;draxin^−/− mice. In this study, Emx1^Cre/+;Z/draxin hetero;draxin^−/− mice are referred to as Ctx-draxin mice and Emx1^+/+;Z/draxin hetero;draxin^−/− mice are referred to as draxin knockout (KO) mice. (b) Immunostaining against EGFP and in situ hybridization for draxin in coronal sections of Ctx-draxin mice showed the specific expression of EGFP and draxin mRNA in the neocortex. Scale bars, 500 μm. (c) draxin mRNA expression detected with in situ hybridization in the neocortex of draxin KO, Ctx-draxin and wild-type mice. Scale bar, 100 μm. (d) Coronal or tangential sections of draxin KO and Ctx-draxin mice stained with calretinin or 5-HT antibodies. Coronal sections of draxin KO and Ctx-draxin mice with DiI injected into the dorsal thalamus. The thalamocortical phenotype was rescued in Ctx-draxin mice (n=5 for each condition). Open arrowheads indicate thalamocortical axons in the neocortex. Scale bars, 500 μm. (e) Coronal sections of draxin KO and Ctx-draxin mice stained with TAG-1 or EGFP antibodies. In draxin KO mice, TAG-1-positive axons did not extend into the internal capsule (arrow). This corticofugal phenotype was rescued in Ctx-draxin mice (arrowhead, n=4 for each condition). Scale bars, 500 μm.