Biochemical non-equivalence of the DSL proteins DLL1 and DLL3 [Elektronische Ressource] / von Insa Geffers

Biochemical non-equivalence of the DSL proteins DLL1 and DLL3 Von der naturwissenschaftlichen Fakultät der Gottfried Wilhelm Leibniz Universität Hannover zur Erlangung des Grades DOKTORIN DER NATURWISSENSCHAFTEN Dr. rer. nat. genehmigte Dissertation von Dipl.-Biochem. Insa Geffers geboren am 24.02.1976 in Wilhelmshaven 2008 Referent: Prof. Dr. Walter Müller Korreferent: Prof. Dr. Achim Gossler Tag der Promotion: 3. März 2008 Abstract Abstract The evolutionary conserved Notch signaling pathway mediates direct communication between adjacent cells and plays a pivotal role in somite formation and patterning during embryogenesis. The Notch ligands Dll1 and Dll3 are both essential for somitogenesis in mammals. However, despite their largely overlapping expression domains in the presomitic mesoderm of mouse embryos, Dll1 and Dll3 null mutant mice display strikingly different somite defects. Additionally, the DLL1 and DLL3 proteins differ with respect to various domains suggesting that both proteins are biochemically not equivalent and exert non-redundant functions during somitogenesis. In this study, it was demonstrated that DLL3 does not induce Notch signaling in transactivation assays. Providing a ‘trivial’ explanation, the DLL3 protein does not localize to the cell surface but accumulates inside the cell.