Knockdown of Foxgl in Sox9+ supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse utricle

Foxg1 plays important roles in regeneration of hair cell (HC) in the cochlea of neonatal mouse. Here, we used Sox9-CreER to knock down Foxgl in supporting cells (SCs) in the utricle in order to investigate the role of Foxg1 in HC regeneration in the utricle. We found Sox9 an ideal marker of utricle SCs and bred Sox9^CreER/+Foxg1^loxp/loxp mice to conditionally knock down Foxgl in utricular SCs. Conditional knockdown (cKD) of Foxgl in SCs at postnatal day one (P01) led to increased number of HCs at P08. These regenerated HCs had normal characteristics, and could survive to at least P30. Lineage tracing showed that a significant portion of newly regenerated HCs originated from SCs in Foxgl cKD mice compared to the mice subjected to the same treatment, which suggested SCs trans-differentiate into HCs in the Foxgl cKD mouse utricle. After neomycin treatment in vitro, more HCs were observed in Foxgl cKD mice utricle compared to the control group. Together, these results suggest that Foxgl cKD in utricular SCs may promote HC regeneration by inducing trans-differentiation of SCs. This research therefore provides theoretical basis for the effects of Foxg1 in trans-differentiation of SCs and regeneration of HCs in the mouse utricle.