Notch signaling in Drosophila requires a RING finger (RF) protein encoded by neuralized. Here we show that the Xenopus homolog of neuralized (Xneur) is expressed where Notch signaling controls cell fate choices in early embryos. Overexpressing XNeur or putative dominant-negative forms in embryos inhibits Notch signaling. As expected for a RF protein, we show that XNeur fulfills the biochemical requirements of ubiquitin ligases. We also show that wild-type XNeur decreases the cell surface level of the Notch ligand, XDelta1, while putative inhibitory forms of XNeur increase it. Finally, we provide evidence that XNeur acts as a ubiquitin ligase for XDelta1 in vitro. We propose that XNeur plays a conserved role in Notch activation by regulating the cell surface levels of the Delta ligands, perhaps directly, via ubiquitination.
PubMed ID: 11740941
Article link: Dev Cell.
Genes referenced: dll1 neurl1 notch1
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|Figure 2. Xneur Expression in Early Xenopus Embryos(A–D) WISH analysis of Xenopus for Xneur RNA expression, shown as dorsal views (A and B), side view (C), or as a transverse section at the level of the spinal cord (D). XneurRNA is expressed within primary neurons in the neural plate ([A–D], black arrowhead) and ciliated cells in the skin ([A–D], white arrowhead). Lower and more diffuse expression of XNeur is detected at stages prior to cell type determination ([A and B], brackets).(E–H) Embryos injected with RNA encoding Notch-ICD (E and F) or Su(H)DBM (G and H) were stained for Xneur RNA by WISH. Arrows and arrowheads indicate primary neurons and ciliated-cell precursors, respectively.|