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lunatic fringe is an essential mediator of somite segmentation and patterning

Nature volume 394, pages 377–381 (1998)Cite this article

Abstract

The gene lunatic fringe encodes a secreted factor with significant sequence similarity to the Drosophila gene fringe1,2,3,4,5. fringe has been proposed to function as a boundary-specific signalling molecule in the wing imaginal disc, where it is required to localize signalling activity by the protein Notch to the presumptive wing margin3,6. By targeted disruption in mouse embryos, we show here that lunatic fringe is likewise required for boundary formation. lunatic fringe mutants fail to form boundaries between individual somites, the initial segmental unit of the vertebrate trunk. In addition, the normal alternating rostral–caudal pattern of the somitic mesoderm is disrupted, suggesting that intersomitic boundary formation and rostral–caudal patterning of somites are mechanistically linked by a process that requires lunatic fringe activity. As a result, the derivatives of the somitic mesoderm, especially the axial skeleton, are severely disorganized in lunatic fringe mutants. Taken together, our results demonstrate an essential function for a vertebrate fringe homologue and suggest a model in which lunatic fringe modulates Notch signalling in the segmental plate to regulate somitogenesis and rostral–caudal patterning of somites simultaneously.

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Figure 1: Expression and targeting of lunatic fringe.
Figure 2: Skeletal phenotype of lunatic fringe mutant mice.
Figure 3: Gross, histological, and immunohistochemical analysis of segmentation in wild-type and lunatic fringe mutant embryos.
Figure 4: Gene expression is altered in the somitic mesoderm of lunatic fringe mutants at 9–9.5 d.p.c
Figure 5: Models for lunatic fringe function during somite segmentation and rostral–caudal patterning.

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Acknowledgements

This work was supported by grants from the German National Merit Foundation (to A.A.), the M.D. Anderson Cancer Center Core, March of Dimes, and the NIH (to R.L.J.). We thank R.Beddington, D. Conner, J. Flanagan, A. Gossler, P. Gruss, F. Guillemot, P. Hasty, D. Henrique, B. Hogan, W. Klein, E. Laufer, Y. Mishina, T. A. Mitsiadis and Y. Saga for reagents, T. Gridley for sharing unpublished results, and R. Behringer and C. Tabin for critical comments on the manuscript.

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Author notes

  1. Yvonne A. Evrard and Yi Lun: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology and Program in Genes and Development, Box 117

    Alexander Aulehla, Lin Gan & Randy L. Johnson

  2. University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, 77030, Texas, USA

    Alexander Aulehla, Lin Gan & Randy L. Johnson

Authors
  1. Yvonne A. Evrard
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Correspondence to Randy L. Johnson.

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Evrard, Y., Lun, Y., Aulehla, A. et al. lunatic fringe is an essential mediator of somite segmentation and patterning. Nature 394, 377–381 (1998). https://doi.org/10.1038/28632

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