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A self-organizing system of repressor gradients establishes segmental complexity in Drosophila

Nature volume 426, pages 849–853 (2003)Cite this article

Abstract

Gradients of regulatory factors are essential for establishing precise patterns of gene expression during development1,2,3; however, it is not clear how patterning information in multiple gradients is integrated to generate complex body plans. Here we show that opposing gradients of two Drosophila transcriptional repressors, Hunchback (Hb) and Knirps (Kni), position several segments by differentially repressing two distinct regulatory regions (enhancers) of the pair-rule gene even-skipped (eve). Computational and in vivo analyses suggest that enhancer sensitivity to repression is controlled by the number and affinity of repressor-binding sites. Because the kni expression domain is positioned between two gradients of Hb, each enhancer directs expression of a pair of symmetrical stripes, one on each side of the kni domain. Thus, only two enhancers are required for the precise positioning of eight stripe borders (four stripes), or more than half of the whole eve pattern. Our results show that complex developmental expression patterns can be generated by simple repressor gradients. They also support the utility of computational analyses for defining and deciphering regulatory information contained in genomic DNA.

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Figure 1: Individual eve stripes are differentially responsive to gradients of Kni and Hb.
Figure 2: Clusters of repressor-binding sites determine enhancer sensitivity.
Figure 3: Mutual repression between Hb and Kni.
Figure 4: Repressor gradients and the generation of pattern complexity.

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Acknowledgements

We thank M. Fujioka and J. Jaynes for transgenic flies containing the eve 4 + 6–lacZ construct; L. Andrioli for discussions and support; A. Oberstein for technical assistance; and C. Desplan, J. Blau and T. Cook for encouragement and comments on the manuscript. D.E.C. was supported by a grant from the NSF. This work was also supported by a grant from the NIH.

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Author notes

  1. Dorothy E. Clyde

    Present address: Biosciences Department, University of Kent, Canterbury, CT2 7NJ, UK

  2. Xuelin Wu

    Present address: Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, 92037, USA

  3. Dorothy E. Clyde and Maria S. G. Corado: These authors contributed equally to this work

Authors and Affiliations

  1. Biology Department, New York University, New York, New York, 10003, USA

    Dorothy E. Clyde, Maria S. G. Corado, Adam Paré, Dmitri Papatsenko & Stephen Small

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  1. Dorothy E. Clyde
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Correspondence to Stephen Small.

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Clyde, D., Corado, M., Wu, X. et al. A self-organizing system of repressor gradients establishes segmental complexity in Drosophila. Nature 426, 849–853 (2003). https://doi.org/10.1038/nature02189

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