A regulator of transcriptional elongation controls vertebrate neuronal development

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 examined. Here we d...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 2000-11, Vol.408 (6810), p.366-369
Main Authors: Rosenthal, Arnon, Guo, Su, Yamaguchi, Yuki, Schilbach, Sarah, Wada, Tadashi, Lee, James, Goddard, Audrey, French, Dorothy, Handa, Hiroshi
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
Animals
Biological and medical sciences
Cell Differentiation - genetics
Cell Differentiation - physiology
Danio rerio
Embryo, Nonmammalian
Fish
Foggy protein
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Developmental
Genes
Isolated neuron and nerve. Neuroglia
Molecular biology
Molecular Sequence Data
Mutation
Neurons
Neurons - physiology
Nuclear Proteins - genetics
Nuclear Proteins - physiology
Proteins
Repressor Proteins - genetics
Repressor Proteins - physiology
Spt5 protein
Transcription Factors - genetics
Transcription Factors - physiology
Transcription, Genetic
Vertebrates
Vertebrates: nervous system and sense organs
Zebrafish
Zebrafish Proteins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 examined. Here we describe the mutant foggy, identified in a genetic screen for mutations that affect neuronal development in zebrafish, 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/35042590