The TLE proteins are the mammalian homologues of Groucho, a member of the Drosophila Notch signaling pathway. Notch signaling controls the differentiation of a variety of tissues in invertebrates and vertebrates. We are investigating the role of the TLE genes during mammalian development. We show that TLE 1 and TLE 3 are expressed during a number of cell-determination events, including embryonic segmentation, central and peripheral neurogenesis, and epithelial differentiation. This expression pattern is in agreement with the involvement of Groucho in similar fate choices in Drosophila and suggests that Groucho and TLE proteins perform similar developmental roles. Our results also show that TLE genes are co-expressed during a variety of cell-fate choices with several vertebrate homologues of genes implicated in the Drosophila Notch cascade, suggesting a role for the TLE proteins in mammalian Notch signaling.