Coherent splicing networks arise from many discrete splicing decisions regulated in unison. Here, we examine the properties of robust, context-specific splicing networks. We propose that a subset of key splicing regulators, or “master splicing factors,” respond to environmental cues to establish and maintain tissue transcriptomes during development.United States. Public Health Service (RO1-GM34277)United States. Public Health Service (R01-CA133404)United States. Public Health Service (U54-CA112967)National Cancer Institute (U.S.) (P30-CA14051