Research Paper Volume 6, Issue 6 pp 496—510

DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells


Figure 8. Unscheduled proliferation is a specific trigger for the DNA damage response in auditory SCs in vitro and in vivo. (A,A') AdcD1-infected P6 cochleas pulsed with EdU (for 24 h between days 2 and 3) and maintained for 3 DIV show accumulation of γH2AX foci in cell cycle reactivated EdU+ Deiters' cells. (B,B') Most EdU+ Deiters' cells show γH2AX downregulation by 7 DIV. (C-E) Cross-sections through the cochlea of a RbloxP/loxP;Fgfr3-iCre-ERT2 mutant mouse at P7 show Ki-67-stained pillar cells (arrowhead in C). γH2AX foci can be seen in pillar cells (arrowhead in D) of mutant, but not control mice. Abbreviations: AdcD1, adenovirus encoding cyclin D1; γH2AX, Ser 139 phosphorylated histone H2AX; co, cochlea; DCs, Deiters' cells; IHC, inner hair cell; OHCs, outer hair cells; IP, inner pillar cell; OP, outer pillar cell; Rb mut, RbloxP/loxP;Fgfr3-iCre-ERT2. Scale bar, shown in E: A-E, 20 µm.