Figure 3. Dystroglycan is required in ventral telencephalon neuroepithelial cells to guide corticothalamic and thalamocortical axons.

L1 staining of P0 brain sections from Dag1^F/+ controls (n = 3 animals) (A, F), Dag1^F/-;Foxg1^Cre (n = 4 animals) (B), Dag1^F/-;Gbx2^CreERT2 (n = 4 animals) (C), Dag1^F/-;Emx1^Cre (n = 3 animals) (D), Dag1^F/-;Dlx5/6^Cre (n = 3 animals) (E), and Dag1^βcyto/- (n = 5 animals) (G). A’-E’ illustrate the recombination patterns in each Cre/CreERT2 line in the blue shaded area. Deletion of Dystroglycan throughout the neuroepithelium of the dorsal and ventral telencephalon in Dag1^F/-;Foxg1^Cre mutants (B, B’) results in abnormal projections in the internal capsule (red arrowheads) and abnormal axonal projections into the upper layers of the cortex (red arrows). Deletion of Dystroglycan from the neuroepithelium of the dorsal telencephalon with Emx1^Cre mutants (D) results in abnormal axonal projections into the upper layers of the cortex (red arrows), but normal internal capsule formation. Deletion of Dystroglycan from the thalamus with Gbx2^CreERT2 (C) or ‘corridor’ cells with Dlx5/6^Cre (E) did not affect axon guidance. Deletion of the intracellular domain of Dystroglycan in Dag1^βcyto/- mutants (G) did not affect formation of the internal capsule compared to control littermates (F). A-G Scale bar = 500 μm.

Figure 3—figure supplement 1. DiI labeling of CTAs and TCAs in Dystroglycan conditional mutants.

(A–E) DiI injections into the cortex (top row) or thalamus (bottom row) of Dystroglycan conditional mutants labels CTAs and TCAs, respectively. CTAs (B) in Dag1^F/-;Foxg1^Cre mutants (n = 3 animals) take an abnormal trajectory through the ventral telencephalon, and TCAs (n = 4 animals) (B’) fail to cross the DTB and instead extend ventrally out of the diencephalon. CTAs in Dag1^F/-;Gbx2^CreERT2 (n = 3 animals) (C), Dag1^F/-;Emx1^Cre (n = 5 animals) (D) and Dag1^F/-;Dlx5/6^Cre (n = 3 animals) (E) mutants are normal, as are TCAs in Dag1^F/-;Gbx2^CreERT2 (n = 4 animals) (C’), and Dag1^F/-;Dlx5/6^Cre (n = 3 animals) (E’) mutants. TCAs in Dag1^F/-;Emx1^Cre (n = 4 animals) (D’) mutants project through the internal capsule normally, but project into the upper layers prematurely upon entering the cortex (red arrows). Scale bar = 500 μm.

Figure 3—figure supplement 2. Recombination pattern in Gbx2^CreERT2 and Emx1^Cre mice.

(A) Gbx2^CreERT2 mice crossed to the AI9; Rosa26^{lox-stop-lox-tdTomato} reporter (n = 2 animals) were dosed with 2.5 mg tamoxifen at e10.5. Analysis of brains at E16 showed recombination of the tdTomato reporter (green) in thalamic neurons/axons. (B) Emx1^Cre mice crossed to the AI9; Rosa26^{lox-stop-lox-tdTomato} reporter (n = 2 animals) showed recombination of the tdTomato reporter (green) in cortical neurons/axons at P0. Scale bar = 500 μm.