The Journal of Neuroscience, October 11, 2006, 26(41):10438-10451; doi:10.1523/JNEUROSCI.1025-06.2006
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Development/Plasticity/Repair
The Transcription Factor six1 Inhibits Neuronal and Promotes Hair Cell Fate in the Developing Zebrafish (Danio rerio) Inner Ear
Olivier Bricaud and
Andres Collazo
Leslie and Susan Gonda (Goldschmied) Cell and Molecular Biology Department, House Ear Institute, Los Angeles, California 90057
Correspondence should be addressed to Olivier Bricaud, Section on Inner Ear Development, Gonda Cell and Molecular Biology Department, House Ear Institute, 2100 West 3rd Street, Los Angeles, CA 90057. E-mail: Email: obricaud{at}hei.org
The developmental processes leading to the differentiation of mechanosensory hair cells and statoacoustic ganglion neurons from the early otic epithelium remain unclear. Possible candidates include members of the PaxSixEyaDach (paired boxsine oculis homeoboxeyes absentdachshund) gene regulatory network. We cloned zebrafish six1 and studied its function in inner ear development. Gain- and loss-of-function experiments show that six1 has opposing roles in hair cell and neuronal lineages. It promotes hair cell fate and, conversely, inhibits neuronal fate by differentially affecting cell proliferation and cell death in these lineages. By independently targeting hair cells with atoh1a (atonal homolog 1a) knockdown or neurons with neurog1 (neurogenin 1) knockdown, we showed that the remaining cell population, neurons or hair cells, respectively, is still affected by gain or loss of six1 function. six1 interacts with other members of the PaxSixEyaDach regulatory network, in particular dacha and dachb in the hair cell but not neuronal lineage. Unlike in mouse, six1 does not appear to be dependent on eya1, although it seems to be important for the regulation of eya1 and pax2b expression in the ventral otic epithelium. Furthermore, six1 expression appears to be regulated by pax2b and also by foxi1 (forkhead box I1) as expected for an early inducer of the otic placode. Our results are the first to demonstrate a dual role for a member of the PaxSixEyaDach regulatory network in inner ear development.
Key words: six1; zebrafish; inner ear; hair cell; neuron; development
Received Nov. 9, 2005;
revised Aug. 25, 2006;
accepted Aug. 27, 2006.
Correspondence should be addressed to Olivier Bricaud, Section on Inner Ear Development, Gonda Cell and Molecular Biology Department, House Ear Institute, 2100 West 3rd Street, Los Angeles, CA 90057. E-mail: Email: obricaud{at}hei.org
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G. Schlosser
How old genes make a new head: redeployment of Six and Eya genes during the evolution of vertebrate cranial placodes
Integr. Comp. Biol.,
September 1, 2007;
47(3):
343 - 359.
[Abstract]
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