mutual inactivation of notch receptors and ligands facilitates developmental patterning相互失活的受体和配体促进发育模式.pdfVIP

Mutual Inactivation of Notch Receptors and Ligands Facilitates Developmental Patterning 1,2. 1,2. 1,2 3 1,2 David Sprinzak , Amit Lakhanpal , Lauren LeBon , Jordi Garcia-Ojalvo , Michael B. Elowitz * 1 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, United States of America, 2 Division of Biology and Department of Applied ´ ` Physics, California Institute of Technology, Pasadena, California, United States of America, 3 Departament de Fısica i Enginyeria Nuclear, Universitat Politecnica de Catalunya, Barcelona, Spain Abstract Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells. Recent work has shown that Notch and Delta, the canonical metazoan juxtacrine signaling receptor and ligand, mutually inactivate each other in the same cell. This cis-interaction generates mutually exclusive sending and receiving states in individual cells. It generally remains unclear, however, how this mutual inactivation and the resulting switching behavior can impact developmental patterning circuits. Here we address this question using mathematical modeling in the context of two canonical pattern formation processes: boundary formation and lateral inhibition. For boundary formation, in a model motivated by Drosophila wing vein patterning, we find that mutual inactivation allows sharp boundary formation across a broader range of parameters than models lacking mutual inactivation.