Defects in somite formation in lunatic fringe-deficient mice

Abstract

Segmentation in vertebrates first arises when the unsegmented paraxial mesoderm subdivides to form paired epithelial spheres called somites1,2. The Notch signalling pathway is important in regulating the formation and anterior–posterior patterning of the vertebrate somite3,4,5,6,7. One component of the Notch signalling pathway in Drosophila is the fringe gene, which encodes a secreted signalling molecule required for activation of Notch during specification of the wing margin8,9,10,11. Here we show that mice homozygous for a targeted mutation of the lunatic fringe (Lfng) gene, one of the mouse homologues12,13 of fringe, have defects in somite formation and anterior–posterior patterning of the somites. Somites in the mutant embryos are irregular in size and shape, and their anterior–posterior patterning is disturbed. Marker analysis revealed that in the presomitic mesoderm of the mutant embryos, sharply demarcated domains of expression of several components of the Notch signalling pathway are replaced by even gradients of gene expression. These results indicate that Lfng encodes an essential component of the Notch signalling pathway during somitogenesis in mice.

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Figure 1: Targeted disruption of the Lfng gene.
Figure 2: Axial truncation and defects in somite formation in LfngLacZ mutant embryos.
Figure 3: Sclerotome and peripheral nervous system defects in LfngLacZ mutant embryos.
Figure 4: Expression of somite lineage markers in wild-type and LfngLacZ mutant embryos.
Figure 5: Expression of markers of the Notch signalling pathway in wild-type and LfngLacZ mutant embryos.

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Acknowledgements

We thank R. Johnson for exchanging unpublished data; C. Norton for doing the blastocyst injections; A. Gossler, R. Jiang and T. O'Brien for comments on the manuscript; and R. Balling, R.Beddington, A. Gossler, B. Hermann, E. Olson and C. Wright for probes. This work was supported by grants from the NIH and the March of Dimes Foundation to T.G., and by a grant from the National Cancer Institute to The Jackson Laboratory.

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Correspondence to Thomas Gridley.

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