Notch receptors generate different types of differentiation signals during development of humans. Accordingly, their loss or aberrant activities result in different types of developmental defects and diseases. To understand the basis for these maladies, and be able to deftly deal with each one of them, we must understand all the different signals generated by these receptors. Drosophila offers an ideal system for the purpose. During differentiation of the central nervous system and epidermis in Drosophila embryos, Notch generates four to five different types of signals. The signals generated to specify the epidermal precursor cells are well understood. However, very little is known about the other types of Notch signals, the intracellular pathways transducing them, or the mechanism by which they are generated. Recent studies show that the full-length Notch receptor, the primary receptor, generates two secondary receptors showing different activities than the primary receptor. The different activities of the three receptors together have the potential to account for all the different types of differentiation signals generated by Notch. The proposed studies will use molecular genetic and biochemical analyses to determine the following. (1) The nature of in vivo signals generated by the different Notch receptors at different stages of differentiation. (2) Whether or not signals from the secondary receptors are transduced by the same pathway that transduces the epidermal precursor cell signals. (3) Whether proteins known to bind Notch regulate the production and activities of the different receptors. These studies are expected to lead to an understanding of how the primary and secondary Notch receptors regulate differentiation of tissues during development.
