Murine Delta homologue, mDelta1, expressed on feeder cells controls cellular differentiation

The Delta/Serrate-Notch pathway is involved in intercellular signaling that controls cell fate during the development of invertebrates and vertebrates . Delta is a prototype of Notch ligands and has been studied extensively in Drosophila, In higher vertebrates, four Delta/Serrate homologues and four Notch homologues have been identified, Recent studies showed that the murin e Delta homologue, mDelta 1, is essential in early embryogenesis. The biolo gical activity of mammalian Delta and its roles in cellular differentiation , however, have remained unclear. In this study, we first surveyed expressi on of mDelta 1 in the adult mouse and found it to be present in a wide rang e of tissues. For testing biological activity of mDelta 1, we expressed a m Delta 1 full-length cDNA in L cells using a eukaryotic expression vector. E ffects of mDelta1 on cellular differentiation were examined in two independ ent systems, featuring C2C12 myogenic differentiation and multipotent murin e bone marrow cell differentiation. Inhibition of the former was observed w ith mDelta1 expression on L cells, associated with suppression of myogenin, a myogenic transcription factor. Expression of mDelta 1 in conjunction wit h GM-CSF promoted differentiation of bone marrow cells to myeloid dendritic cells at the expense of other lineages. Although the effects of mDelta 1 o n two differentiation systems appeared opposing, as inhibition occurring in one and induction in the other, this can be understood by the unifying con cept of generation of diverse cell types from equivalent progenitors, Thus, the present study provided evidence that mammalian Delta participates in i ntercellular signaling, determining the cell fate in a wide variety of tiss ues.