An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells.
P19 cells, a mouse embryonal carcinoma line, can be induced to differentiate into neurons. After induction, however, only a small subpopulation of cells develop as neurons, suggesting that equipotent cells adopt different cell fates. In invertebrate systems, the lin-12-Notch family of genes is thought to control the choice of cell fate. We have therefore asked whether activation of murine Notch (mNotch) regulates neuronal differentiation in P19 cells. We demonstrate that a dominant gain-of-function mutant of mNotch suppresses neurogenesis, as well as myogenesis in P19 cells. Overexpression of the full-length mNotch protein also suppresses neurogenesis. In contrast, the differentiation of glia is not affected by an activated mNotch homologue. These data indicate that mNotch may play a central role in the choice of cell fate in differentiating cells in culture and suggests that mNotch may play a similar role in the choice of fate in the developing mammalian embryo.
Department of Biochemistry, Columbia University, New York, New York 10032.
J S
JS
Nye
R
R
Kopan
R
R
Axel
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009132:Muscles / Q000166:cytology*; D009420:Nervous System / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors