Figure 3.

Mitochondrial dysfunction impairs multiple steps in the neurogenic process during cortical development. (A and B) Representative confocal images and quantification of proliferation of NPCs in E15.5 control and AIF knockouts using PH3 (phosphohistone 3; M-phase marker) and BrdU (S-phase marker) labeling. Data presented as mean and SD (n = 3 independent samples). (C and D) Representative confocal images and quantification of Tbr2+ progenitors and DCX+ neuroblasts co-labeled with Ki67 (proliferation marker) in E15.5 control and AIF knockouts. Data presented as mean and SD (n = 3 independent samples). (E and F) Representative confocal images and quantification of Tbr2+ progenitors and DCX+ neuroblasts co-labeled with Ki67 in E12.5 control and AIF knockouts. Data presented as mean and SD (n = 3 independent samples). (G–I) Representative confocal images following 48 h of in utero electroporation of GFP at E13.5 in the dorsal forebrain of control and AIF knockouts. Scale = 50 μm. Quantification of GFP+ cells based on location within the dorsal cortex (F) and co-labeling with DCX (G). Results are represented as mean and SD (n = 3 independent samples). (J) AIF control and knockout cells derived from E15.5 dorsal cortex were plated as monolayers and subjected to an in vitro differentiation assay. Cells were exposed to a 1-h BrdU pulse prior to fixation at 1 and 5 days in vitro (DIV). Data presented as mean and SD (n = 3 independent samples). *P < 0.05; **P < 0.01; ***P < 0.001 (Student’s t-test).