Article
- The EMBO Journal (2004) 23, 3041 - 3050
- doi:10.1038/sj.emboj.7600307
Published online: 15 July 2004
Subject Categories:
Nicalin and its binding partner Nomo are novel Nodal signaling antagonists
Christof Haffner1, Mélanie Frauli1, Stephanie Topp1,2,3, Martin Irmler4, Kay Hofmann4, Jörg T Regula5, Laure Bally-Cuif2,3 and Christian Haass1
- Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Munich, Germany
- Zebrafish Neurogenetics Research Group, Department of Virology, Technical University-Munich, Munich, Germany
- GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, Neuherberg, Germany
- Bioinformatics Group, MEMOREC Biotech GmbH, Cologne, Germany
- Adolf-Butenandt-Institute, Protein Analysis Unit, Ludwig-Maximilians-University, Munich, Germany
Correspondence to:
Christof Haffner, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Schillerstr. 44, 80336 Munich, Germany. Tel.: +49 89 5996 484; Fax: +49 89 5996 415; E-mail: chaffner@med.uni-muenchen.de
Christian Haass, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Adolf-Butenandt-Institute, Ludwig-Maximilians-University, Schillerstr. 44, 80336 Munich, Germany. Tel.: +49 89 5996 474; Fax: +49 89 5996 415; E-mail: chaass@med.uni-muenchen.de
Received 22 January 2004; Accepted 8 June 2004
Abstract
Nodals are signaling factors of the transforming growth factor-
(TGF) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated 
-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish.
Keywords:
- Lefty,
- mesoderm,
- Nicastrin,
- Nodal,
- pM5
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