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Nature
Article
License: implied-oa
Data sources: UnpayWall
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PubMed Central
Other literature type . 2009
Data sources: PubMed Central
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Nature
Article . 2009 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
Nature
Article . 2009
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Gene regulatory logic of dopamine neuron differentiation

Authors: Flames, Nuria; Hobert, Oliver;

Gene regulatory logic of dopamine neuron differentiation

Abstract

Dopamine signalling regulates a variety of complex behaviours, and defects in dopamine neuron function or survival result in severe human pathologies, such as Parkinson's disease. The common denominator of all dopamine neurons is the expression of dopamine pathway genes, which code for a set of phylogenetically conserved proteins involved in dopamine synthesis and transport. Gene regulatory mechanisms that result in the direct activation of dopamine pathway genes and thereby ultimately determine the identity of dopamine neurons are poorly understood in all systems studied so far. Here we show that a simple cis-regulatory element, the dopamine (DA) motif, controls the expression of all dopamine pathway genes in all dopaminergic cell types in Caenorhabditis elegans. The DA motif is activated by the ETS transcription factor AST-1. Loss of ast-1 results in the failure of all distinct dopaminergic neuronal subtypes to terminally differentiate. Ectopic expression of ast-1 is sufficient to activate the dopamine pathway in some cellular contexts. Vertebrate dopamine pathway genes also contain phylogenetically conserved DA motifs that can be activated by the mouse ETS transcription factor Etv1 (also known as ER81), and a specific class of dopamine neurons fails to differentiate in mice lacking Etv1. Moreover, ectopic Etv1 expression induces dopaminergic fate marker expression in neuronal primary cultures. Mouse Etv1 can also functionally substitute for ast-1 in C. elegans. Our studies reveal a simple and apparently conserved regulatory logic of dopamine neuron terminal differentiation and may provide new entry points into the diagnosis or therapy of conditions in which dopamine neurons are defective.

Related Organizations
Keywords

Neurons, Dopamine, Neurogenesis, Nerve Tissue Proteins, Regulatory Sequences, Nucleic Acid, Olfactory Bulb, Article, DNA-Binding Proteins, Evolution, Molecular, Mice, Gene Expression Regulation, Animals, Cell Lineage, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cells, Cultured, Conserved Sequence, Heat-Shock Response, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
219
Top 1%
Top 10%
Top 1%
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