International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr. Gerhard Przemeck
GSF-National Research Centre
Institute of Experimental Genetics
Ingolstaedter Landstr. 1
Neuherberg D-85764

Co-Authors: 1) Heinzmann U, 2) Beckers J, 2)Hrabé de Angelis M
Institutions: 1) GSF - Institute of Pathology; 2) GSF - Institute of Experimental Genetics

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. Delta/Notch signalling, which had not been implicated in this morphogenetic process so far, is known to be required, for example, for proper somitogenesis, normal differentiation of pancreatic endocrine cells and inner ear sensory development. Here, we report that Delta/Notch signalling is also 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 from the node. Interestingly, we find that Delta/Notch signalling is also required for the proper differentiation of node cells and node morphology.

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