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Publication : Notch signaling regulates left-right asymmetry determination by inducing Nodal expression.

First Author  Krebs LT Year  2003
Journal  Genes Dev Volume  17
Issue  10 Pages  1207-12
PubMed ID  12730124 Mgi Jnum  J:83358
Mgi Id  MGI:2661305 Doi  10.1101/gad.1084703
Citation  Krebs LT, et al. (2003) Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev 17(10):1207-12
abstractText  Generation of left-right asymmetry is an integral part of the establishment of the vertebrate body plan. Here we show that the Notch signaling pathway plays a primary role in the establishment of left-right asymmetry in mice by directly regulating expression of the Nodal gene. Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry. Analysis of the enhancer regulating node-specific Nodal expression revealed the presence of binding sites for the RBP-J protein, the primary transcriptional mediator of Notch signaling. Mutation of these sites destroyed the ability of this enhancer to direct node-specific gene expression in transgenic mice. Our results demonstrate that Dll1-mediated Notch signaling is essential for generation of left-right asymmetry, and that the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice.
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