A regulator of transcriptional elongation controls vertebrate neuronal development

Su Guo, Yuki Yamaguchi, Sarah Schilbach, Tadashi Wada, James Lee, Audrey Goddard, Dorothy French, Hiroshi Handa and Arnon Rosenthal
Additional contact information
Su Guo: University of California
Yuki Yamaguchi: Frontier Collaborative Research Center (FCRC) and Department of Biological Information Tokyo Institute of Technology 4259 Nagatsuta
Sarah Schilbach: Departments of Molecular Biology and Pathology
Tadashi Wada: Frontier Collaborative Research Center (FCRC) and Department of Biological Information Tokyo Institute of Technology 4259 Nagatsuta
James Lee: Departments of Molecular Biology and Pathology
Audrey Goddard: Departments of Molecular Biology and Pathology
Dorothy French: Genentech Inc.
Hiroshi Handa: Frontier Collaborative Research Center (FCRC) and Department of Biological Information Tokyo Institute of Technology 4259 Nagatsuta
Arnon Rosenthal: Departments of Molecular Biology and Pathology

Nature, 2000, vol. 408, issue 6810, 366-369

Abstract: Abstract The development of distinct vertebrate neurons is defined by the unique profiles of genes that neurons express. It is accepted that neural genes are regulated at the point of transcription initiation, but the role of messenger RNA elongation in neural gene regulation has not been examined1,2,3. Here we describe the mutant foggy, identified in a genetic screen for mutations that affect neuronal development in zebrafish4, that displayed a reduction of dopamine-containing neurons and a corresponding surplus of serotonin-containing neurons in the hypothalamus. Positional cloning disclosed that Foggy is a brain-enriched nuclear protein that is structurally related to the transcription elongation factor Spt5 (refs 5,6,7,8,9,10,11 ,12). Foggy is not part of the basic transcription apparatus but a phosphorylation-dependent, dual regulator of transcription elongation. The mutation disrupts its repressive but not its stimulatory activity. Our results provide molecular, genetic and biochemical evidence that negative regulators of transcription elongation control key aspects of neuronal development.

Date: 2000
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DOI: 10.1038/35042590

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