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© Marion Coolen
Radial glia neural stem cells of the adult zebrafish telencephalon electroporated with a membrane tagged GFP
Publication : The EMBO journal

Nicalin and its binding partner Nomo are novel Nodal signaling antagonists

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The EMBO journal - 15 Jul 2004

Haffner C, Frauli M, Topp S, Irmler M, Hofmann K, Regula JT, Bally-Cuif L, Haass C

Link to Pubmed [PMID] – 15257293

EMBO J. 2004 Aug;23(15):3041-50

Nodals are signaling factors of the transforming growth factor-beta (TGFbeta) 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 gamma-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.

http://www.ncbi.nlm.nih.gov/pubmed/15257293