Fgf and Hh Signalling Act on a Symmetrical Pre-Pattern to Specify Anterior and Posterior Identity in the Zebrafish Otic Placode and Vesicle

Department of Biomedical Science, The University of Sheffield, Sheffield, England, United Kingdom
Development (Impact Factor: 6.46). 09/2011; 138(18):3977-87. DOI: 10.1242/dev.066639
Source: PubMed


Specification of the otic anteroposterior axis is one of the earliest patterning events during inner ear development. In zebrafish, Hedgehog signalling is necessary and sufficient to specify posterior otic identity between the 10 somite (otic placode) and 20 somite (early otic vesicle) stages. We now show that Fgf signalling is both necessary and sufficient for anterior otic specification during a similar period, a function that is completely separable from its earlier role in otic placode induction. In lia(-/-) (fgf3(-/-)) mutants, anterior otic character is reduced, but not lost altogether. Blocking all Fgf signalling at 10-20 somites, however, using the pan-Fgf inhibitor SU5402, results in the loss of anterior otic structures and a mirror image duplication of posterior regions. Conversely, overexpression of fgf3 during a similar period, using a heat-shock inducible transgenic line, results in the loss of posterior otic structures and a duplication of anterior domains. These phenotypes are opposite to those observed when Hedgehog signalling is altered. Loss of both Fgf and Hedgehog function between 10 and 20 somites results in symmetrical otic vesicles with neither anterior nor posterior identity, which, nevertheless, retain defined poles at the anterior and posterior ends of the ear. These data suggest that Fgf and Hedgehog act on a symmetrical otic pre-pattern to specify anterior and posterior otic identity, respectively. Each signalling pathway has instructive activity: neither acts simply to repress activity of the other, and, together, they appear to be key players in the specification of anteroposterior asymmetries in the zebrafish ear.

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    • "A previous study showed that Fgf signaling was required for anterior identity (marked by expression of pax5) of the otic vesicle [45]. Fgf3 was identified as a ligand in part responsible for regionalizing the otic vesicle, however only a partial loss of pax5 mRNA was observed. "
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    • "NeuroD(þ) neuroblasts are fully committed to the neuronal fate, migration to, and proliferation within the CVG (Alsina et al., 2004). Data from FGF-GOF experiments in the zebrafish using a heatshock inducible FGF3 (hsp70:FGF3) transgenic line clearly demonstrate that FGF signaling is sufficient for neurogenesis and delamination in the otic vesicle (Hammond and Whitfield, 2011). Delaminating NeuroD( þ) neuroblasts are increased in the anteroventral domain and also ectopically expressed from the nonneural posteroventral otic domain. "
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    • "This suggests that the growth of the S otolith is tightly regulated during development so that the otolith grows to an appropriate size for acoustic sensory transduction. Previous studies indicate that the genes involved in OV patterning and hair cell formation are differentially expressed along the antero-posterior axis in the developing ear272829. Further studies are required to clarify whether these genes, or other genes and molecules, contribute to macular-specific protein synthesis or secretion processes that in turn contribute to otolith development. "
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