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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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
signal transduction; lefty; mesoderm; nicastrin; nodal; pM5
ISSN (print) / ISBN
0261-4189
e-ISSN
1460-2075
Zeitschrift
EMBO Journal, The
Quellenangaben
Band: 23,
Heft: 15,
Seiten: 3041-3050
Verlag
Wiley
Verlagsort
Heidelberg, Germany
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Developmental Genetics (IDG)