Structure and distribution of the Notch protein in developing Drosophila.

Antibodies to Notch show that it is a stable, high-molecular-weight transmembrane glycoprotein, with epidermal growth factor (EGF)-like elements exposed on the cell surface. The protein is phosphorylated variably on serines of the cytoplasmic domain. Individual Notch polypeptide chains appear to be associated with one another by disulfide bonds, suggesting that homotypic interaction of these proteins is required for function. Immunocytochemistry has revealed striking features of Notch expression that might clarify its function: Cells of the ventral neurogenic ectoderm become conspicuously labeled with the protein prior to embryonic neurogenesis, and Notch appears to be associated with cells destined for both neural and epidermal lineages. High levels of Notch become restricted to neuroblasts as they delaminate from the embryonic ectoderm and are apposed to mesoderm. Mesodermal cells express Notch also, suggesting a possible involvement in neurogenesis, or an unknown role in mesoderm differentiation. In larvae and pupae, a correlation of expression and neuroblast mitotic activity is seen for many cells. Notch produced by a dividing neuroblast may persist on derivative cells, including terminally differentiated neurons and nerve processes. In the larval eye imaginal disk, strong Notch expression appears in the morphogenetic furrow, uniformly on cell surfaces as they cluster to form ommatidia. Expression persists on ommatidia after release from the furrow. These patterns suggest a role for Notch in position-dependent development in both initiation and maintenance of cell-surface interactions. In the eye and embryonic ectoderm, uniform expression on cells interacting to produce different developmental lineages from a single primordium suggests that Notch alone may not be sufficient to elaborate cell fates.