Abstract: Novel soluble Notch receptor ligands and polynucleotides encoding such are disclosed, as well as methods for producing and using these novel nucleotides and polypeptides. These novel polypeptides or agonists or antagonists thereto modulate cellular activity, regulate the growth and division of cell, including stem cells, progenitor and precursor cells, are involved in cell fate decisions, and provide prophylactic or therapeutic benefits for treatment of human diseases. Expression systems are provided that facilitate the production, secretion, and purification of these molecules.