Figure 4. Ablation of BMPRII in neural progenitor cells promotes hippocampal neurogenesis and reduces anxiety- and depression-like behaviors.

(a) Experimental paradigm: BMPRII^fx/fx; Ascl1-CreER™; Rosa^ZG/ZG mice (KO) were administered tamoxifen for five consecutive days in order to ablate the BMP type II receptor in neural progenitor cells. BMPRII^+/+; Ascl1-CreER™; Rosa^ZG/ZG littermates were used as wild type (WT) controls. Behavior was assessed on the elevated zero maze (EZM) and open field (OF) tests on day 14 and on the tail suspension test (TST) on day 15. On day 16 mice were sacrificed (Sac) and tissue was harvested for immunohistochemical analysis. (b) Immunostaining for the neuronal marker NeuN demonstrates that there is an increase in the number of recombined cells (ZG+) that have differentiated into neurons in the BMPRII KO mice compared to WT controls. (c) Quantification of the number of ZG+NeuN+ cells per mm³ in the dentate gyrus shows that there is an increase in neurogenesis in the BMPRII KO mice. n=8 per group. (d) Knockout of BMPRII increased the latency to immobility in the TST. n=8 per group. (e) Knockout of BMPRII decreased the total time spent immobile in the TST. n=8 per group. (f) The percentage of time spent in the open arms of the EZM is higher in BMPRII KO mice compared to BMPRII WT controls. n=8 per group. (g) No difference was observed between WT and BMPRII KO groups in the total distance traveled in the open field. n=8 per group. (h) In the open field, BMPRII knockout led to an increase in the percentage of distance traveled in the center of the arena rather than the periphery. n=8 per group.

Data are presented as mean±SEM. Unpaired Student’s t-test: *p<0.05, **p<0.01, ***p<0.001. Scale bar: 50µm