The Role of gfi1.2 in the Development of Zebrafish Inner Ear

Inner ear hair cells are mechanosensitive cells responsible for sensing and transmitting signals to the brain to be interpreted as sound or head position/movement. The zinc-finger protein, gfi1, is expressed in differentiating neurons and inner ear hair cells. Gfi1 deficiency leads to a massive loss of cochlear hair cells in mice. However, the mechanism remains unclear. To develop an effective molecular therapy for hearing loss, it is critical to first understand the relationship between gfi1 and hair cell development. We demonstrated in the zebrafish model that gfi1.2 was initially expressed in the inner ear at 14 hours post-fertilization (hpf), preceding the expression of gfi1.1 at 19 hpf. In the morpholino-mediated gfi1.2 knockdown mutants, hair cells reduced in number without altering the expression of pax2a, dlx3b, atho1a and pou4f3, the markers for otic patterning and specification. There was a down-regulation of the pro-neuronal genes, ngn1 and atoh1b in the context of gfi1.2 knockdown, which was rescued by the exogenous gfi1.2. We also found that gfi1.2 may regulate ngn1 expression by suppressing id2a. Our results suggested that knockdown of gfi1.2 may lead to deafness through promoting cells proliferation in the pro-sensory region and interrupting cell differentiation.