Notch Signaling in the Salivary Gland. A.S. Haberman ¹, E. Knust ², D. Andrew ¹. 1) Dept Cell Biol & Anatomy, Johns Hopkins Univ Sch Med, Baltimore, MD; 2) University of Duesseldorf, Germany.

   We are studying the development of the embryonic salivary glands as a model for organogenesis. The salivary glands have two major cell types: duct cells and secretory cells. The duct cells express and require TRACHEALESS (TRH), a transcription factor that functions in a complex with TANGO (TGO) to regulate expression of downstream target genes. One such target gene in the salivary duct is Serrate (Ser), one of the two known ligands for the NOTCH (N) receptor. Using electrophoretic mobility shift assays, we have identified three TRH/TGO binding sites in two Ser promoter fragments that direct salivary duct expression. We are currently testing the importance of these sequences in TRH dependent salivary duct expression. We are also exploring the role of Ser in the salivary gland. Loss-of-function Serrate mutants have on average 15% fewer duct cells than wild type. Embryos carrying the Beaded of Goldschmidt mutation, an allele of Serrate that encodes a truncated product that acts as a general inhibitor of N signaling, have on average 85% fewer duct cells and severely reduced secretory cells. Similarly, N mutants have 95% fewer duct cells and secretory cells. These data support two potential, non-exclusive models. In the first model, Serrate expression in the duct cells is necessary to protect the pool of cells determined to be salivary duct from being recruited to a neuronal fate. In model two, Serrate is required to direct or maintain duct cells fate. To test these models, we are marking the cells of the early duct with Ser-lacZ expression and observing their fates in Serrate mutants. If model I is correct, lacZ-expressing cells will be found in the CNS. If model II is correct, lacZ-expressing cells will be found in the secretory portion of the salivary gland.