title: Understanding signaling dynamics through synthesis.
abstract: Tissue-scale organization emerges from the action of sophisticated multiscale                    developmental programs. But the design rules for composing elementary signaling                    and information processing modules into such functional systems and for                    integrating them into the noisy and convoluted living context remain                    incompletely addressed. The construction of a synthetic gene circuit encoding                    contact-dependent signal propagation demonstrates one broadly applicable                    approach to this problem. The circuit comprises orthogonal signaling through the                    Delta ligand and the Notch receptor, multicellular positive feedback, and                    transcriptional signal amplification. Positive feedback and contact signaling                    proved sufficient for bistability and signal propagation across a population of                    mammalian cells, but only when combined with signal amplification. Thus,                    construction and characterization of synthetic gene circuits have made it                    possible to establish mechanistic sufficiency and the minimal requirements for                    the phenotype of interest.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Slusarczyk
authors.forename: Ron
authors.initials: R
authors.lastname: Weiss
mesh_terms: D002450:Cell Communication; D025461:Feedback, Physiological; D006801:Humans; D051880:Receptors, Notch; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D051880:Receptors, Notch