Notch receptors involved in the choice between intestinal secretory and enterocytes and differentiation of Bestrophin 4 cells.

During the first half of embryogenesis, the intestinal epithelium is a simple layer of cuboidal cells surrounded by lateral plate splanchnic mesoderm. As embryogenesis proceeds, the epithelium differentiates to include a variety of enterocytes and secretory cells. During the period of epithelial cell differentiation a number of signaling pathways are used to generate the full complement of cell types. Notch signaling is important for the choice between enterocytes and secretory cells. Following the initial choice, both enterocytes and secretory cells continue differentiating into a number of different subtypes of each cell type. In the zebrafish embryo, Notch signaling is utilized at least three times during development of the intestinal epithelium. The first two Notch signaling events are involved in the choice between enterocytes and secretory cells, while the third involves differentiation of a unique cell type that we previously called Notch Receiving Secretory Cells (NRSCs). While we have identified the times when Notch signaling is active, the individual Notch receptors used in each signaling event have not been previously identified. Here we use loss of function mutants in the four Notch receptors (