title: Fgf and Hh signalling act on a symmetrical pre-pattern to specify anterior and posterior identity in the zebrafish otic placode and vesicle.
abstract: 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.
authors.affiliation: MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Hammond
authors.forename: Tanya T
authors.initials: TT
authors.lastname: Whitfield
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics*; D004423:Ear / Q000196:embryology* / Q000502:physiology; D007758:Ear, Inner / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D051518:Fibroblast Growth Factor 3; D053823:Hedgehog Proteins; D011758:Pyrroles; C105686:SU 5402; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; D005346:Fibroblast Growth Factors