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Published online
doi:10.1083/jcb.200702009
The Journal of Cell Biology, Vol. 178, No. 3, 465-476
The Rockefeller University Press, 0021-9525 $30.00
© Geffers et al.
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Article

Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo



Insa Geffers1, Katrin Serth1, Gavin Chapman3, Robert Jaekel4, Karin Schuster-Gossler1, Ralf Cordes1, Duncan B. Sparrow3, Elisabeth Kremmer2, Sally L. Dunwoodie3, Thomas Klein4, and Achim Gossler1

1 Institut für Molekularbiologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany
2 Forschungszentrum für Umwelt und Gesundheit, Institut für Molekulare Immunologie, 81377 München, Germany
3 The Victor Chang Cardiac Research Institute, University of New South Wales, Darlinghurst NSW 2010, Australia
4 Institut für Genetik, Universität zu Köln, 50674 Köln, Germany

Correspondence to Achim Gossler: gossler.achim{at}mh-hannover.de

The Notch ligands Dll1 and Dll3 are coexpressed in the presomitic mesoderm of mouse embryos. Despite their coexpression, mutations in Dll1 and Dll3 cause strikingly different defects. To determine if there is any functional equivalence, we replaced Dll1 with Dll3 in mice. Dll3 does not compensate for Dll1; DLL1 activates Notch in Drosophila wing discs, but DLL3 does not. We do not observe evidence for antagonism between DLL1 and DLL3, or repression of Notch activity in mice or Drosophila. In vitro analyses show that differences in various domains of DLL1 and DLL3 individually contribute to their biochemical nonequivalence. In contrast to endogenous DLL1 located on the surface of presomitic mesoderm cells, we find endogenous DLL3 predominantly in the Golgi apparatus. Our data demonstrate distinct in vivo functions for DLL1 and DLL3. They suggest that DLL3 does not antagonize DLL1 in the presomitic mesoderm and warrant further analyses of potential physiological functions of DLL3 in the Golgi network.

I. Geffers and K. Serth contributed equally to this paper.

Abbreviations used in this paper: A-P, anterior–posterior; E, embryonic day; ICD, intracellular domain; PSM, presomitic mesoderm; TM, transmembrane domain.


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