CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.
J Neurosci
; 24(50): 11215-25, 2004 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-15601927
ABSTRACT
Homeodomain proteins play critical roles during development in cell fate determination and proliferation, but few studies have defined gene regulatory networks for this class of transcription factors in differentiated cells. Using a lacZ-knock-in strategy to ablate Nkx6-2, we find that the Nkx6-2 promoter is active embryonically in neuroblasts and postnatally in oligodendrocytes. In addition to neurological deficits, we find widespread ultrastructural abnormalities in CNS white matter and aberrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contactin. The involvement of these downstream proteins in cytoskeletal function and cell adhesion reveals mechanisms whereby Nkx6-2 directly or indirectly regulates axon- glial interactions at myelin paranodes. Nkx6-2 does not appear to be the central regulator of axoglial junction assembly; nonetheless, our data constitute the first evidence of such a regulatory network and provide novel insights into the mechanism and effector molecules that are involved.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Sistema Nervoso Central
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Proteínas de Homeodomínio
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Junções Intercelulares
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Bainha de Mielina
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article