Repression of Hedgehog signalling is required for the acquisition of dorsolateral cell fates in the zebrafish otic vesicle.
In zebrafish, Hedgehog (Hh) signalling from ventral midline structures is necessary and sufficient to specify posterior otic identity. Loss of Hh signalling gives rise to mirror symmetric ears with double anterior character, whereas severe upregulation of Hh signalling leads to double posterior ears. By contrast, in mouse and chick, Hh is predominantly required for dorsoventral otic patterning. Whereas a loss of Hh function in zebrafish does not affect dorsoventral and mediolateral otic patterning, we now show that a gain of Hh signalling activity causes ventromedial otic territories to expand at the expense of dorsolateral domains. In a panel of lines carrying mutations in Hh inhibitor genes, Hh pathway activity is increased throughout the embryo, and dorsolateral otic structures are lost or reduced. Even a modest increase in Hh signalling has consequences for patterning the ear. In ptc1(-/-) and ptc2(-/-) mutant embryos, in which Hh signalling is maximal throughout the embryo, the inner ear is severely ventralised and medialised, in addition to displaying the previously reported double posterior character. Transplantation experiments suggest that the effects of the loss of Hh pathway inhibition on the ear are mediated directly. These new data suggest that Hh signalling must be kept tightly repressed for the correct acquisition of dorsolateral cell fates in the zebrafish otic vesicle, revealing distinct similarities between the roles of Hh signalling in zebrafish and amniote inner ear patterning.
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Katherine L
KL
Hammond
Fredericus J M
FJ
van Eeden
Tanya T
TT
Whitfield
D000818:Animals; D000906:Antibodies / Q000032:analysis; D002645:Chickens; D003094:Collagen / Q000235:genetics / Q000276:immunology; D017931:DNA Primers; D007758:Ear, Inner / Q000033:anatomy & histology / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000276:immunology / Q000502:physiology; D006309:Hearing / Q000502:physiology*; D006454:Hemoglobins / Q000235:genetics / Q000502:physiology; D051379:Mice; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012665:Semicircular Canals / Q000033:anatomy & histology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*
D000906:Antibodies; D017931:DNA Primers; D006454:Hemoglobins; D003094:Collagen