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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Nicalin and its binding partner Nomo are novel nodal signaling antagonists.
EMBO J. 23, 3041-3050 (2004)
Nodals are signaling factors of the transforming growth factor‐β (TGFβ) 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 γ‐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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
signal transduction; lefty; mesoderm; nicastrin; nodal; pM5
ISSN (print) / ISBN
0261-4189
e-ISSN
1460-2075
Journal
EMBO Journal, The
Quellenangaben
Volume: 23,
Issue: 15,
Pages: 3041-3050
Publisher
Wiley
Publishing Place
Heidelberg, Germany
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)