Abstract
The establishment of the main body axis and the determination of left–right asymmetry are fundamental aspects of vertebrate embryonic development. A link between these processes has been revealed by the frequent finding of midline defects in humans with left–right anomalies1. This association is also seen in a number of mutations in mouse2,3,4 and zebrafish1,5, and in experimentally manipulated Xenopus embryos5. However, the severity of laterality defects accompanying abnormal midline development varies6, and the molecular basis for this variation is unknown. Here we show that mouse embryos lacking the early-response gene SIL have axial midline defects, a block in midline Sonic hedgehog (Shh) signalling and randomized cardiac looping. Comparison with Shh mutant embryos7, which have axial defects but normal cardiac looping, indicates that the consequences of abnormal midline development for left–right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2 .
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Acknowledgements
We thank H. Westphal and N. Takuma for Shh knockout mice; A.-M. Walsh and staff for generation of chimaeras; J. Magrath and R. Mollina for animal care; G. Miller for pathology on teratomas; R. Dryfus for photography; P. Thomas for technical help; P. Aplan, H. Hamada, A. Joyner, C.Chiang, H. Hahn and M. Blum for providing probes; and M. Halpern, H. Arnheiter and B. Casey for comments on the manuscript.
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Izraeli, S., Lowe, L., Bertness, V. et al. The SIL gene is required for mouse embryonic axial development and left–right specification. Nature 399, 691–694 (1999). https://doi.org/10.1038/21429
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DOI: https://doi.org/10.1038/21429
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