International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 43 - NODE AND MIDLINE DEFECTS ARE ASSOCIATED WITH LEFT-RIGHT DEVELOPMENT IN DELTA1 MUTANT EMBRYOS

G Przemeck
GSF – National Research Centre for Environment & Health

Heinzmann U, Beckers J Hrabe de Angelis M
GSF – National Research Centre for Environment & Health

Axes formation is a fundamental process of early embryonic development. In addition to the antero-posterior and dorso-ventral axes, the determination of the left-right (L/R) axis is crucial for the proper morphogenesis of internal organs and is a distinctive feature of vertebrates. Genes known to be required for the normal establishment and/or maintenance of L/R asymmetry in mammals include, for example, components of the TGF-b family of intercellular signalling molecules and genes required for node cilia function. Here, we report that Delta/Notch signalling, which had not been implicated in this morphogenetic process so far, is required for normal L/R determination in mice. We show that the loss-of-function of the Delta1 gene causes a situs ambiguous phenotype including randomisation of the orientation of heart looping and embryonic turning. A possible cause for this L/R defect in Delta1 mutant embryos is a failure in the development of proper midline structures. These originate form the node. Accordingly, we find that Delta/Notch signalling is also required for the proper differentiation of node cells and node morphology.


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