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PMID:15456880

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Citation

Pönniö, T and Conneely, OM (2004) nor-1 regulates hippocampal axon guidance, pyramidal cell survival, and seizure susceptibility. Mol. Cell. Biol. 24:9070-8

Abstract

The nuclear receptor transcription factor, nor-1, is expressed during mammalian development predominantly in the nervous system and is induced in a cell-specific manner in nonneuronal cells in response to a variety of extracellular stimuli. To elucidate the essential developmental functions of this transcription factor, we have analyzed the consequences of its elimination on central nervous system development in mice. Here we show that null mutant mice lacking nor-1 respond with increased limbic seizure activity to the excitotoxic glutamate receptor agonist kainic acid. We demonstrate that these abnormalities are associated with defective postnatal hippocampal development exemplified by abnormal axonal guidance of dentate gyrus granule and mossy cells, disorganization of the pyramidal cell layer, and early postnatal death of pyramidal neurons in the CA1 field of the hippocampus. Our data indicate that nor-1 plays a critical role in neuronal survival and axonal guidance in the developing murine hippocampus and that hippocampal dysgenesis in nor-1-/- mice may be an underlying cause of seizure susceptibility.

Links

PubMed PMC517886 Online version:10.1128/MCB.24.20.9070-9078.2004

Keywords

Animals; Axons/metabolism; Cell Movement/physiology; Cell Survival; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Disease Susceptibility; Excitatory Amino Acid Agonists/pharmacology; Hippocampus/cytology; Hippocampus/growth & development; Kainic Acid/pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nuclear Receptor Subfamily 4, Group A, Member 1; Nuclear Receptor Subfamily 4, Group A, Member 2; Pyramidal Cells/cytology; Pyramidal Cells/drug effects; Pyramidal Cells/metabolism; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Receptors, Thyroid Hormone; Seizures/chemically induced; Seizures/metabolism; Transcription Factors/metabolism

Significance

Annotations

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

MOUSE:NR4A3

acts_upstream_of_or_within

GO:0021766: hippocampus development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3037444

P

  • results_in_development_of:(EMAPA:35409)

Seeded From UniProt

complete

MOUSE:NR4A3

acts_upstream_of_or_within

GO:0007411: axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3037444

P

  • occurs_in:(EMAPA:35409)

Seeded From UniProt

complete

MOUSE:NR4A3

acts_upstream_of_or_within

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3037444

P

  • occurs_in:(EMAPA:35409)
  • regulates_o_occurs_in:(CL:0000598)

Seeded From UniProt

complete


See also

References

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