A regulator of transcriptional elongation controls vertebrate neuronal development

The development of distinct vertebrate neurons is defined by the unique pro files of genes that neurons express. It is accepted that neural genes are r egulated at the point of transcription initiation, but the role of messenge r RNA elongation in neural gene regulation has not been examined(1-3). Here we describe the mutant foggy, identified in a genetic screen for mutations that affect neuronal development in zebrafish(4), that displayed a reducti on of dopamine-containing neurons and a corresponding surplus of serotonin- containing neurons in the hypothalamus. Positional cloning disclosed that F oggy is a brain-enriched nuclear protein that is structurally related to th e transcription elongation factor Spt5 (refs 5-12). Foggy is not part of th e basic transcription apparatus but a phosphorylation-dependent, dual regul ator of transcription elongation. The mutation disrupts its repressive but not its stimulatory activity. Our results provide molecular, genetic and bi ochemical evidence that negative regulators of transcription elongation con trol key aspects of neuronal development.