Abstract
The mechanism controlling the development of dopaminergic (DA) and serotonergic (5HT) neurons in vertebrates is not well understood. Here we characterized a zebrafish mutant—too few (tof)—that develops hindbrain 5HT and noradrenergic neurons, but does not develop hypothalamic DA and 5HT neurons. tof encodes a forebrain-specific zinc finger transcription repressor that is homologous to the mammalian Fezl (forebrain embryonic zinc finger–like protein). Mosaic and co-staining analyses showed that fezl was not expressed in DA or 5HT neurons and instead controlled development of these neurons non-cell-autonomously. Both the eh1-related repressor motif and the second zinc finger domain were necessary for tof function. Our results indicate that tof/fezl is a key component in regulating the development of monoaminergic neurons in the vertebrate brain.
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Acknowledgements
We thank T. Yabe, S. Neuhauss, C. Liew, C. Ton, A. Jensen, G. Wilhelm Otto, T. Look and M. Austen for sharing their unpublished mapping information and R. Geisler and E. Goldings for providing the above contact information; M. Ekker, A. Schier, U. Strahle, P. Raymonds and S. Wilson for probes; S. Guo, K. Poulsen and L. Parker for technical advice; T. Hirano for support and comments on this work, and members of the Rosenthal lab for stimulating discussions. G.L. was supported by a long-term postdoctoral fellowship from the European Molecular Biology Organization. W.S.T. was supported by National Institutes of Health grant RR12349.
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Levkowitz, G., Zeller, J., Sirotkin, H. et al. Zinc finger protein too few controls the development of monoaminergic neurons. Nat Neurosci 6, 28–33 (2003). https://doi.org/10.1038/nn979
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DOI: https://doi.org/10.1038/nn979
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