To send or receive but not both: An inter-cellular signaling switch for multi-cellular pattern formation

David Sprinzak,

California Institute of Technology 
How complex patterns of cells are generated during embryonic development has been a central question in science for centuries. In the past few decades many of the molecular components involved in these processes (signaling molecules, genes, and proteins) and their interactions have been identified. While we can use this knowledge to draw a detailed interaction network of genes and proteins, it is often unclear how these genetic networks generate the observed patterns. In this talk, I will describe the experimental and theoretical analysis of a class of developmental processes that lead to ‘fine grained’ patterns: patterns with a typical length scale of one cell (e.g. alternating patterns of cell fates or sharp boundaries between regions of cells). In animals, many of these fine grained patterns rely on the Notch signaling pathway which is the canonical communication system between neighboring cells. We use quantitative time lapse microscopy of mammalian cells together with mathematical modeling to study how the properties of the Notch signaling pathway affect pattern formation. We show how the Notch signaling pathway integrates extracellular and intracellular signals to generate a sharp switch between two mutually exclusive signaling states; a ‘sender’ state in which a cell can predominantly send signals, and a ‘receiver’ state in which a cell predominantly ‘receives’ signals. Furthermore, we show how this signaling switch can play an important role in the differentiation of neighboring cells into distinct fates in several developmental patterning processes. Finally, I will describe how the experimental and theoretical approach developed in this study can be generalized to address a variety of basic questions in developmental patterning that cannot easily be investigated with standard biological techniques.