| dc.description.abstract | During early inner ear development, patterning of the sensory and neural domains is established in response to multiple signaling inputs. Although the importance of Fgf, Wnt, and Hh for inner ear development have been established, coordination of the signals is still poorly understood. Here, we have examined how these signals impact development of the vestibular sensory domain, auditory sensory domain, and neurogenic domain and identified downstream targets which mediate this process.
In zebrafish, the sensory and neural domains form simultaneously in the adjacent medial and lateral regions, respectively, of the otic vesicle. We used transgenic and pharmacological methods to alter Fgf and Wnt signaling during early placodal stages and then examined changes in patterning and growth. Blocking Fgf reduced cell proliferation and eliminated both sensory and neural development. Although Wnt promoted cell proliferation, it was not required for either sensory or neural development. Sustained overactivation of Wnt, however, led to expansion of sensory and medial markers at the expense of lateral and neurogenic markers. We found that pax2a, sp5a, and sp5l are co-regulated by Fgf and Wnt. Additionally, they are required for some aspects of sensory development and for Wnt to properly suppress neurogenesis.
The otic vesicle contains two sensory maculae, the utricle and saccule, which develop concurrently and acquire distinct vestibular and auditory function by 3 and 5 days post fertilization, respectively. We investigated the roles of Fgf and Hh in development of the utricle and saccule using pharmacological and transgenic methods.
pax5, a transcription factor exclusively expressed in the developing utricle, required Fgf and was limited to the anterior domain by Hh. pou3f3b, a transcription factor uniquely expressed in the developing saccule, required Hh but also had an early requirement for fgf8a and was restricted at later stages by fgf3. The Fgf-target gene pax2a was required for expression of both pax5 and pou3f3b and expression of pax2a was not maintained in the otic vesicle without Fgf and Hh. Thus, Fgf and Hh govern expression of pax5 and pou3f3b and could regulate functional divergence of the utricle and saccule. | |
