Dispensable role of Rac1 and Rac3 after cochlear hair cell specification

AbstractRac small GTPases play important roles during embryonic development of the inner ear; however, little is known regarding their function in cochlear hair cells (HCs) after specification. Here, we revealed the localization and activation of Racs in cochlear HCs using GFP-tagged Rac plasmids and transgenic mice expressing a Rac1-fluorescence resonance energy transfer (FRET) biosensor. Furthermore, we employedRac1-knockout (Rac1-KO,Atoh1-Cre;Rac1flox/flox) andRac1 andRac3 double KO (Rac1/Rac3-DKO,Atoh1-Cre;Rac1flox/flox;Rac3−/−) mice, under the control of theAtoh1 promoter. However, bothRac1-KO andRac1/Rac3-DKO mice exhibited normal cochlear HC morphology at 13  weeks of age and normal hearing function at 24 weeks of age. No hearing vulnerability was observed in young adult (6-week-old)Rac1/Rac3-DKO mice even after intense noise exposure. Consistent with prior reports, the results fromAtoh1-Cre;tdTomato mice confirmed that theAtoh1 promoter became functional only after embryonic day 14 when the sensory HC precursors exit the cell cycle. Taken together, these findings indicate that although Rac1 and Rac3 contribute to the early development of sensory epithelia in cochleae, as previously shown, they are dispensable for the maturation of cochlear HCs in the postmitotic state or for hearing maintenance following HC maturation.Key messagesMice with Rac1 and Rac3 deletion were generated after HC specification.Knockout mice exhibit normal cochlear hair cell morphology and ...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research