Figure 4

Misrouting of dopaminergic axons in Pbx1-deficient embryos. TH immunohistochemistry on E15 coronal (A, B) and E14 sagittal sections (E, F), and on E13 dissected brains in whole mount preparation (C-D’) of wild type (A, C, E) and Pbx1−/− mutant embryos (B, D. F). (A, B) Distribution of mesDA neurons in the ventral midbrain is identical in wild type and Pbx1−/− mice. (C-D’) E13 whole mount preparation of isolated neural tube. TH-positive neurons are located in the ventral midbrain (arrowheads) of wild type (C) and Pbx1-deficient (D) embryos. Wild type TH-positive axons have reached deep into the ventral telencephalon, whereas the Pbx1−/− axons have prematurely stopped their growth prior to entry of the ganglionic eminence and begin to defasciculate at the tip (arrow) (D, D’). C’ and D’ are higher magnification of the dashed box in C and D. (E, F) At E14, the bundle of TH-positive axons is compact, fasciculated and directed towards the ventral telencephalon in the wild type (E). In the mutants, the axon bundle is wider and disorganized (arrow) and shows misrouted axonal tips (arrowheads) (F). Dorsal to the top, C-F rostral to the left. Scale bars A, B = 200 μm, C, D, E, F = 500 μm and C’, D’ = 250 μm. mesDA: mesencephalic dopaminergic.