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PMID:10360575

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Citation

Pattyn, A, Morin, X, Cremer, H, Goridis, C and Brunet, JF (1999) The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399:366-70

Abstract

The sympathetic, parasympathetic and enteric ganglia are the main components of the peripheral autonomic nervous system, and are all derived from the neural crest. The factors needed for these structures to develop include the transcription factor Mash1, the glial-derived neurotrophic factor GNDF and its receptor subunits, and the neuregulin signalling system, each of which is essential for the differentiation and survival of subsets of autonomic neurons. Here we show that all autonomic ganglia fail to form properly and degenerate in mice lacking the homeodomain transcription factor Phox2b, as do the three cranial sensory ganglia that are part of the autonomic reflex circuits. In the anlagen of the enteric nervous system and the sympathetic ganglia, Phox2b is needed for the expression of the GDNF-receptor subunit Ret and for maintaining Mash1 expression. Mutant ganglionic anlagen also fail to switch on the genes that encode two enzymes needed for the biosynthesis of the neurotransmitter noradrenaline, dopamine-beta-hydroxylase and tyrosine hydroxylase, demonstrating that Phox2b regulates the noradrenergic phenotype in vertebrates.

Links

PubMed Online version:10.1038/20700

Keywords

Animals; Autonomic Nervous System/embryology; Basic Helix-Loop-Helix Transcription Factors; DNA-Binding Proteins/metabolism; Dopamine beta-Hydroxylase/genetics; Enteric Nervous System/embryology; Enteric Nervous System/physiology; Ganglia, Autonomic/embryology; Ganglia, Autonomic/physiology; Ganglia, Sensory/embryology; Ganglia, Sensory/physiology; Gene Expression; Gene Targeting; Genes, Homeobox; Glial Cell Line-Derived Neurotrophic Factor; Homeodomain Proteins/genetics; Homeodomain Proteins/physiology; Mice; Mutagenesis, Insertional; Nerve Growth Factors; Nerve Tissue Proteins/genetics; Neural Crest/cytology; Neural Crest/embryology; Neural Crest/physiology; Proto-Oncogene Proteins/genetics; Receptor, Epidermal Growth Factor/genetics; Receptor, erbB-3; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription Factors/physiology; Tyrosine 3-Monooxygenase/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PHX2B

involved_in

GO:0003357: noradrenergic neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PHX2B

involved_in

GO:0048486: parasympathetic nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PHX2B

involved_in

GO:0048485: sympathetic nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PHX2B

involved_in

GO:0048484: enteric nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PHX2B

involved_in

GO:0071542: dopaminergic neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PHX2B

involved_in

GO:1901166: neural crest cell migration involved in autonomic nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ASCL1

involved_in

GO:0048486: parasympathetic nervous system development

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ASCL1

involved_in

GO:0048485: sympathetic nervous system development

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ASCL1

involved_in

GO:0048484: enteric nervous system development

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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