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Updated: Jul 6, 2026

Loss- and Gain-of-function Approach to Investigate Early Cell Fate Determinants in Preimplantation Mouse Embryos
Published on: June 6, 2016
The neogenin intracellular domain regulates gene transcription via nuclear translocation
David Goldschneider1, Nicolas Rama, Catherine Guix
1Apoptosis, Cancer, and Development Laboratory, Equipe Labellisée La Ligue, CNRS UMR5238, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
Abstract:
Neogenin is a multifunctional receptor implicated in axon navigation, neuronal differentiation, morphogenesis, and cell death. Very little is known about signaling downstream of neogenin. Because we found that the neogenin intracellular domain (NeICD) interacts with nuclear proteins implicated in transcription regulation, we investigated further whether neogenin signals similarly to the Notch receptor. We show here that neogenin is cleaved by gamma-secretase, an event that releases the complete NeICD. We also describe that NeICD is located at the nucleus, a feature regulated through a balance between nuclear import and export. NeICD triggers gene reporter transactivation and associates with nuclear chromatin. Direct transcriptional targets of NeICD were determined and were shown to be up-regulated in the presence of neogenin ligand. Together, we reveal here a novel aspect of neogenin signaling that relies on the direct implication of its intracellular domain in transcriptional regulation.
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