Cloning and characterization of Sel-11, a murine homolog of the C-elegans sel-1 gene

The Notch signaling pathway regulates specification and proliferation in a variety of cell lineages in invertebrates and vertebrates. We have cloned a murine homolog of SEL-1, a key negative regulator of the Notch pathway in Caenorhabditis elegans. Murine SEL-1L (mSEL-1L) protein exhibits a high deg ree of similarity to SEL-1, including a signal peptide and the C-terminal r egion required for SEL-1 function in C. elegans. This mammalian homolog of sel-1 is widely expressed in adult mouse and human tissues, with particular ly high levels in the pancreas. RNA in situ analysis of developing mouse em bryos indicates that mSEL-1L is moderately expressed throughout the neural tube and dorsal root ganglia, with particularly high levels in the floor pl ate of the neural tube beginning at E10.5 and increasing at E11.5. Expressi on is high at E14.5 and E17.5 in the acini of the pancreas, and moderate in the epithelial cells of the gut villi. We localized the SEL-1L protein to the cytosol, possibly in intracellular vesicles, in a beta-islet-derived tu mor cell line (RinM). (C) 1998 Elsevier Science Ireland Ltd. All rights res erved.