Fig. 7. Otx2 controls proliferation and post-mitotic transition of mesDA progenitors. (A-H) Representative adjacent sections through the intermediate mesencephalon of E10.5 (A-D) and E11.5 (E-H) wild-type and En1^Cre/+; Otx2^flox/flox embryos immunostained with Nkx6.1 and BrdU (A,B,E,F), Nkx2.2 and BrdU (C,D,G,H), and then stained with Hoechst show that the number of BrdU⁺ cells is dramatically and selectively reduced in the mesDA domain of mutants. (I-L) Graphic representation showing the AP graded reduction of the LI in the mesDA domain of mutants (I,J), whereas the LI measured in the Nkx2.2⁺ domain of mutant embryos is similar to that detected in the Nkx6.1⁺ domain of control embryos (K,L). (M-P) Representative adjacent sections through the intermediate mesencephalon of E11.5 wild-type and En1^Cre/+; Otx2^flox/flox mutants immunostained with Ki67 and BrdU (M,N), and Nkx2.2 and Nkx6.1 (O,P) show that, in mutant embryos, Ki67 is switched off in the majority of mesDA progenitors and that most of the mesDA BrdU⁺ cells (labeled at E10.5) become post-mitotic (Ki67^-) at E11.5. Conversely, in the Nkx2.2⁺ domain, most of the BrdU⁺ progenitors retain Ki67 expression as in the Nkx6.1⁺ domain of control embryos. (Q,R) Graphic representation of the Qfs in the mesDA (Q), Nkx6.1⁺ (in wild type) and Nkx2.2⁺ (in En1^Cre/+; Otx2^flox/flox embryos) domains (R) shows a selective increase in the number of mesDA progenitors quitting the cell-cycle in mutant embryos, whereas a mild reduction is detected in the Nkx2.2⁺ domain. The arrow and the broken line in (A-H,M-P) indicate the Nkx6.1⁺ or the Nkx2.2⁺ territories analyzed. Abbreviations: Ant., anterior; Int., intermediate; Post., posterior.