International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

MONDAY 10 NOVEMBER
11:45 – 12:00 HRS

IDENTIFICATION OF NOVEL DELTA/NOTCH TARGET GENES DURING MOUSE EMBRYONIC DEVELOPMENT USING DNA-CHIP AND PROTEIN EXPRESSION PROFILING

Machka C
Institute of Experimental Genetics, GSF Research Center for Environment and Health

Co-Authors: 2) Halder T, 2) Harder A, 1) Hrabe de Angelis M, 1) Beckers J
Institutions: 1) Institute of Experimental Genetics, GSF Research Center for Environment and Health, 2) TopLab GmbH, Martinsried

The Delta/Notch signal transduction pathway is conserved between many species. During the embryonic development of the mouse the Delta/Notch pathway is involved in diverse patterning processes: lateral specification during neurogenesis and pancreatic development, left/right organization and involvement in processes like the synchronization/organization of the segmentation clock and establishment and maintenance of somite boundaries during somitogenesis are some of them. Only a few of these developmental processes can be explained adequately by the classical Delta/Notch pathway model describing lateral inhibition. In order to identify novel targets of Delta1 on RNA, as well as protein level, we started to screen transcriptome and proteome using DNA-chip technology and 2D-gelelectrophoresis combined with mass spectrometry of Delta1 (Dll1)-deficient and Dll1-wildtype embryos at E10.5. Until now we have identified 26 upregulated and 20 downregulated genes using a DNA chip containing more than 20.000 genes. 22 of the identified candidate genes with differential gene expression are known genes with assigned functions while 24 are unknown genes. Using 2D-gelelectrophoresis 1 upregulated and 15 downregulated proteins have been identified (pH 4-7) so far. To analyse their potential involvement in Delta/Notch signalling we systematically carried out whole mount in situ hybridisations. Using this scanning method we identified a subset of genes expressed in tissues where Delta/Notch signalling is functionally required, e.g. in the somitic and presomitic mesoderm and neural tissues. Data of the most promising candidates will be presented.


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