Progression from mitotic catastrophe to germ cell death in Caenorhabditis elegans lis-1 mutants requires the spindle checkpoint.
Dev Biol
; 305(2): 397-410, 2007 May 15.
Article
em En
| MEDLINE
| ID: mdl-17376425
ABSTRACT
Deletion of the lissencephaly disease gene LIS-1 in humans causes an extreme disorganization of the brain associated with significant reduction in cortical neurons. Here we show that deletion or RNA interference (RNAi) of Caenorhabditis elegans lis-1 results in a reduction in germline nuclei and causes a variety of cellular, developmental, and neurological defects throughout development. Our analysis of the germline defects suggests that the reduction in nuclei number stems from dysfunctional mitotic spindles resulting in cell cycle arrest and eventually programmed cell death (apoptosis). Deletion of the spindle checkpoint gene mdf-1 blocks lis-1(lf)-induced cell cycle arrest and germline apoptosis, placing the spindle checkpoint pathway upstream of the programmed cell death pathway. These results suggest that apoptosis may contribute to the cell-sparse pathology of lissencephaly.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espermatozoides
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Deleção de Genes
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Caenorhabditis elegans
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Apoptose
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Proteínas de Ciclo Celular
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Proteínas de Caenorhabditis elegans
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Proteínas Associadas aos Microtúbulos
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Mitose
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Fuso Acromático
Limite:
Animals
Idioma:
En
Revista:
Dev Biol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos