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Fates-shifted is an F-box protein that targets Bicoid for degradation and regulates developmental fate determination in Drosophila embryos

Nature Cell Biology volume 13, pages 22–29 (2011)Cite this article

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Abstract

Bicoid (Bcd) is a morphogenetic protein that instructs patterning along the anterior–posterior (A–P) axis in Drosophila melanogaster embryos. Despite extensive studies, what controls the formation of a normal concentration gradient of Bcd remains an unresolved and controversial question. Here, we show that Bcd protein degradation is mediated by the ubiquitin-proteasome pathway. We have identified an F-box protein, encoded by fates-shifted (fsd), that has an important role in Bcd protein degradation by targeting it for ubiquitylation. Embryos from females lacking fsd have an altered Bcd gradient profile, resulting in a shift of the fatemap along the A–P axis. Our study is an experimental demonstration that, contrary to an alternative hypothesis, Bcd protein degradation is required for normal gradient formation and developmental fate determination.

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Figure 1: Bcd is degraded through the proteasome-dependent pathway.
Figure 2: Bcd is ubiquitylated.
Figure 3: Fsd has a role in Bcd protein degradation.
Figure 4: Fsd interacts with both Skp1 and Bcd.
Figure 5: Posterior shift of fatemap along the A–P axis in fsd embryos.
Figure 6: Bcd gradient profiles in wild-type and fsd embryos.

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Acknowledgements

We thank members of our groups at CCHMC, in particular F. He, D. Cheung, W. Dui, and J. Deng, for discussion and assistance, and we thank Xinhua Lin's lab for some of the primers used in our dsRNAi screening. This work was supported in part by grants from NIH and NSF (to J.M.).

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Authors and Affiliations

  1. Division of Biomedical Informatics, Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, 45229, OH, USA

    Junbo Liu & Jun Ma

  2. Division of Developmental Biology, Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, 45229, OH, USA

    Jun Ma

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  1. Junbo Liu
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J.L. and J.M. conceived and designed the study. J.L. performed all experiments and analysis. J.L. and J.M. interpreted the data, J.L. generated all figures and J.L. and J.M. wrote the paper.

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Correspondence to Jun Ma.

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Liu, J., Ma, J. Fates-shifted is an F-box protein that targets Bicoid for degradation and regulates developmental fate determination in Drosophila embryos. Nat Cell Biol 13, 22–29 (2011). https://doi.org/10.1038/ncb2141

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