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The zebrafish mutation m865 affects formation of dopaminergic neurons and neuronal survival, and maps to a genetic interval containing the sepiapterin reductase locus

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Abstract

The zebrafish mutation m865 was isolated during a large-scale mutagenesis screen aimed at identifying genes involved in the development and maintenance of subgroups of neurons in the zebrafish central nervous system. The phenotype of m865 mutant embryos shows defects in the development of dopaminergic neurons in the pretectum and of retinal amacrine cells, as well as abnormal caudal dopaminergic cluster in the diencephalon. The effects of the mutation appear not to be restricted to dopaminergic neurons, as development of other neurotransmitter systems (serotonergic and cholinergic) is impaired as well. Furthermore, increased apoptosis is localized to the m865 mutant retina and in the optic tectum starting at 24hpf, and may lead to the observed reduced size of the mutant head and eye. Early patterning is not affected in m865 mutant embryos, and expression of genes known to play a role in dopaminergic cell differentiation is normal except for reduced expression of nurr1 in the mutant retina. Thus the m865 mutation does not specifically affect dopaminergic neuron development. m865 was genetically mapped to linkage group 5, and the critical genomic interval could be narrowed down to a region of 110 kb, containing four candidate genes. For one of these candidate genes, sepiapterin reductase (spr), a requirement for neuronal survival has previously been implicated, including dopaminergic neurons. Identification of the mutated gene should lead to a more detailed understanding of the defects observed in m865 mutant embryos, and potentially could enhance the understanding of the development and maintenance of specific dopaminergic neuronal populations.

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Abbreviations

dpf:

Days post fertilization

hpf:

Hours post fertilization

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Acknowledgments

We are grateful to Dr. Johannes Bischof, Dr. Katrin Dürr, Dr. Soojin Ryu and Björn Wendik for advice during mutant analysis and cloning; Dr. Jörg Rauch, Dr. Robert Geisler, Silke Geiger-Rudoph (Max-Planck-Insitut für Entwicklungsbiologie, Tübingen) and Dr. Heinz-Georg Belting for advice on genetic mapping; Dr. Hans-Georg Fronhöfer (Max-Planck-Insitut für Entwicklungsbiologie, Tübingen) for providing tm88z fish. We thank Franziska Seifert and Sabine Götter for technical assistance and fish care; Dr. Max Muenke for discussion. This work was supported through DFG-SFB 505 B7 (WD).

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  1. Department of Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, 79104, Freiburg, Germany

    Anne-Kathrin Ettl, Jochen Holzschuh & Wolfgang Driever

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  1. Anne-Kathrin Ettl
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Correspondence to Wolfgang Driever.

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Ettl, AK., Holzschuh, J. & Driever, W. The zebrafish mutation m865 affects formation of dopaminergic neurons and neuronal survival, and maps to a genetic interval containing the sepiapterin reductase locus. Brain Struct Funct 211 (Suppl 1), 73–86 (2006). https://doi.org/10.1007/s00429-006-0128-7

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