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Comparative analysis of her genes during fish somitogenesis suggests a mouse/chick-like mode of oscillation in medaka

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Somitogenesis is the key developmental step, which divides the vertebrate body axis into segmentally repeated structures. It requires an intricate process of pre-patterning, which is driven by an oscillator mechanism consisting of the Delta–Notch pathway and various hairy- and Enhancer of split-related (her) genes. The subset of her genes, which are necessary to set up the segmentation clock, reveal a complex scenario of interactions. To understand which her genes are essential core players in this process, we compared the expression patterns of somitogenesis-relevant her genes in zebrafish and medaka (Oryzias latipes). Most of the respective medaka genes (Ol-her) are duplicated like what has been shown for zebrafish (Dr-her) and pufferfish genes (Fr-her). However, zebrafish genes show some additional copies and significant differences in expression patterns. For the paralogues Dr-her1 and Dr-her11, only one copy exists in the medaka (Ol-her1/11), which combines the expression patterns found for both zebrafish genes. In contrast to Dr-her5, the medaka orthologue appears to play a role in somitogenesis because it is expressed in the presomitic mesoderm (PSM). PSM expression also suggests a role for both Ol-her13 genes, homologues of mouse Hes6 (mHes6), in this process, which would be consistent with a conserved mHes6 homologue gear in the segmentation clock exclusively in lower vertebrates. Members of the mHes5 homologue group seem to be involved in somite formation in all vertebrates (e.g. Dr- and Ol-her12), although different paralogues are additionally recruited in zebrafish (e.g. Dr-her15) and medaka (e.g. Ol-her4). We found that the linkage between duplicates is strongly conserved between pufferfish and medaka and less well conserved in zebrafish. Nevertheless, linkage and orientation of several her duplicates are identical in all three species. Therefore, small-scale duplications must have happened before whole genome duplication occurred in a fish ancestor. Expression of multiple stripes in the intermediate PSM, characteristic for the zebrafish orthologues, is absent in all somitogenesis-related her genes of the medaka. In fact, the expression mode of Ol-her1/11 and Ol-her5 indicates dynamism similar to the hairy clock genes in chicken and mouse. This suggests that Danio rerio shows a rather derived clock mode when compared to other fish species and amniotes or that, alternatively, the clock mode evolved independently in zebrafish, medaka and mouse or chicken.

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The authors wish to thank Diethard Tautz, Julian Lewis and Jean-Nicolas Volff for critically reading the manuscript and Manfred Schartl for fruitful discussions and support. Furthermore, the authors from the Department of Evolutionary Genetics thank Diethard Tautz for his generous and constant support of this research project. Genome data have been provided freely by the National Institute of Genetics and the University of Tokyo for use in this publication only. We wish to thank Eva Schetter for excellent technical assistance and David and Carsten for fish care. We are very grateful to Drs. Makoto-Furutani Seiki and Hisato Kondoh for providing the medaka somite mutants. The authors would also like to thank an unknown reviewer for his/her very helpful comments and constructive criticism. The work was supported by the Deutsche Forschungsgemeinschaft (SFB 572) and by the Fond der chemischen Industrie.

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Correspondence to Martin Gajewski.

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"M. Gajewski and M. Girschick contributed equally to this work." Communicated by M. Hammerschmidt

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Gajewski, M., Elmasri, H., Girschick, M. et al. Comparative analysis of her genes during fish somitogenesis suggests a mouse/chick-like mode of oscillation in medaka. Dev Genes Evol 216, 315–332 (2006).

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  • Somitogenesis
  • bHLH transcription factor
  • her genes
  • medaka
  • Cyclic gene expression