Nicalin and its binding partner Nomo are novel Nodal signaling antagonists

作者: Christof Haffner , Mélanie Frauli , Stephanie Topp , Martin Irmler , Kay Hofmann

DOI: 10.1038/SJ.EMBOJ.7600307

关键词: Nodal signalingLeftyNodal signaling pathwayCell fate determinationBiologyEctopic expressionGeneticsCell biologyNODALZebrafishTransforming growth factor betaGeneral Biochemistry, Genetics and Molecular BiologyGeneral Immunology and MicrobiologyGeneral NeuroscienceMolecular biology

摘要: Nodals are signaling factors of the transforming growth factor-β (TGFβ) superfamily with a key role in vertebrate development. They control variety cell fate decisions required for establishment embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), novel antagonists Nodal signaling. is distantly related to Nicastrin, component Alzheimer's disease-associated γ-secretase, forms complex Nomo. Ectopic expression both proteins zebrafish embryos causes cyclopia, phenotype that can arise from defect mesendoderm patterning mediated by pathway. Accordingly, downregulation resulted an increase anterior axial development enlarged hatching gland. Inhibition ectopic Lefty was rescued reducing levels. Furthermore, Nodal- well Activin-induced inhibited cell-based reporter assay. Our data demonstrate Nicalin/Nomo antagonizes during mesendodermal zebrafish.

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