Abstract
During development of the zebrafish inner ear, regional patterning in the ventral half of the otic vesicle establishes zones of gene expression that correspond to neurogenic, sensory and non-neural cell fates. FGF and Retinoic acid (RA) signalling from surrounding tissues are known to have an early role in otic placode induction and otic axial patterning, but how external signalling cues are translated into intrinsic patterning during otic vesicle (OV) stages is not yet understood. FGF and RA signalling pathway members are expressed in and around the OV, suggesting important roles in later patterning or maintenance events. We have analysed the temporal requirement of FGF and RA signalling for otic development at stages after initial anteroposterior patterning has occurred. We show that high level FGF signalling acts to restrict sensory fates, whereas low levels favour sensory hair cell development; in addition, FGF is both required and sufficient to promote the expression of the non-neural marker otx1b in the OV. RA signalling has opposite roles: it promotes sensory fates, and restricts otx1b expression and the development of non-neural fates. This is surprisingly different from the earlier requirement for RA signalling in specification of non-neural fates via tbx1 expression, and highlights the shift in regulation that takes place between otic placode and vesicle stages in zebrafish. Both FGF and RA signalling are required for the development of the otic neurogenic domain and the generation of otic neuroblasts. In addition, our results indicate that FGF and RA signalling act in a feedback loop in the anterior OV, crucial for pattern refinement.
Highlights
Most cell types of the inner ear arise from the otic placode, a region of specialised ectoderm lying adjacent to the developing hindbrain
Expression of fibroblast growth factor (FGF) and Retinoic acid (RA) signalling pathway members in the zebrafish otic vesicle To address the role of FGF and RA signalling in otic patterning at otic vesicle (OV) stages, we first examined the expression of pathway members in and around the OV from 18 hours post fertilisation/18 somites (18 hpf/18S)
At 26 hpf, expression of fgfr4 is excluded from the neurogenic region, but remains strongly expressed at the OV poles. fgfr1a and fgfr2 are expressed in the posterior part of the OV weakly from slightly after the onset of otx1b expression (22S) and expression persists at 26 hpf
Summary
Most cell types of the inner ear arise from the otic placode, a region of specialised ectoderm lying adjacent to the developing hindbrain. To form the complex three-dimensional structure of the adult inner ear, cells in the otic region integrate information from both extrinsic and intrinsic factors over time, thereby gradually restricting the competence of the different regions in the emerging inner ear. In the developing zebrafish otic vesicle (OV), one of the first subdivisions to occur is the emergence of sensory, neurogenic and non-neural domains in the ventral otic epithelium. The sensory domain gives rise to the sensory patches or maculae at the anterior and posterior poles of the OV, consisting of sensory hair cells and supporting cells. Neurons of the statoacoustic ganglion (SAG) arise from the neurogenic domain in an anteroventral position. The non-neural domain, located ventrolaterally, gives rise to non-neural epithelium, including the ventral pillar of the lateral semicircular canal
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
