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PMID:18786357

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Citation

Nóbrega-Pereira, S, Kessaris, N, Du, T, Kimura, S, Anderson, SA and Marín, O (2008) Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors. Neuron 59:733-45

Abstract

The homeodomain transcription factor Nkx2-1 plays key roles in the developing telencephalon, where it regulates the identity of progenitor cells in the medial ganglionic eminence (MGE) and mediates the specification of several classes of GABAergic and cholinergic neurons. Here, we have investigated the postmitotic function of Nkx2-1 in the migration of interneurons originating in the MGE. Experimental manipulations and mouse genetics show that downregulation of Nkx2-1 expression in postmitotic cells is necessary for the migration of interneurons to the cortex, whereas maintenance of Nkx2-1 expression is required for interneuron migration to the striatum. Nkx2-1 exerts this role in the migration of MGE-derived interneurons by directly regulating the expression of a guidance receptor, Neuropilin-2, which enables interneurons to invade the developing striatum. Our results demonstrate a role for the cell-fate determinant Nkx2-1 in regulating neuronal migration by direct transcriptional regulation of guidance receptors in postmitotic cells.

Links

PubMed PMC2643060 Online version:10.1016/j.neuron.2008.07.024

Keywords

Animals; Cell Count/methods; Cell Differentiation/physiology; Cell Movement/physiology; Chromatin Immunoprecipitation/methods; Electroporation/methods; Embryo, Mammalian; Gene Expression Regulation, Developmental/physiology; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Interneurons/physiology; LIM-Homeodomain Proteins; Luminescent Proteins/genetics; Luminescent Proteins/metabolism; Median Eminence/cytology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neuropilin-2/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/physiology; Organ Culture Techniques; Transcription Factors/genetics; Transcription Factors/physiology

Significance

Annotations

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

MOUSE:NKX21

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_regulation_target:(MGI:MGI:1100492)

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(MGI:MGI:1100492)

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0022029: telencephalon cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3653645

P

  • occurs_in:(EMAPA:17549)
  • results_in_movement_of:(CL:0000099)

Seeded From UniProt

complete

MOUSE:NKX21

acts_upstream_of_or_within

GO:0021795: cerebral cortex cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(EMAPA:17544)
  • results_in_movement_of:(CL:0000099)

Seeded From UniProt

complete

MOUSE:NKX21

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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