Aberrant apoptosis in the neurological mutant Flathead is associated with defective cytokinesis of neural progenitor cells.
Brain Res Dev Brain Res
; 130(1): 53-63, 2001 Sep 23.
Article
em En
| MEDLINE
| ID: mdl-11557093
ABSTRACT
Flathead is a rat neurological mutant which is phenotypically characterized by a flattened cranium, resting tremor, ataxia, progressive paralysis of the hind limbs, and death at 3-4 weeks after birth. Previous studies showed that rats homozygous for the mutation have a dramatically reduced brain size caused by a burst of apoptosis that begins after embryonic day 16 (E16) and which peaks at about E18. Late-developing structures such as the dentate gyrus, internal granule layer of the cerebellum, and superficial layers of the neocortex are severely depleted of cells. In the present study we have found that neurons and glia are both affected by the mutation. Immunohistochemical analysis with TAG-1, a marker for migratory neurons, revealed reduced staining in Fh neocortex and cerebellum, indicating that the mutation affects neuronal migration or a developmental event prior to it. Analysis of acutely dissociated neocortical cultures showed an accumulation of nestin-positive progenitor cells. Moreover, a substantial proportion of these progenitor cells were multinucleated with the nuclei organized as rosettes. Such multinucleated cells were also found in intact sections of the neocortex and the cerebellum where their presence was restricted to proliferative zones. Within the neocortex, the abundance of multinucleated progenitors is highest at E18 and decreases thereafter, thus correlating with the profile of cell death. This, along with the dramatically higher frequency of apoptosis among multinucleated cells, suggests that the aberrant cell death in Fh is due to defective cytokinesis that occurs in progenitor cells during late stages of brain development.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_congenital_chromosomal_anomalies
Assunto principal:
Células-Tronco
/
Moléculas de Adesão Celular Neuronais
/
Cerebelo
/
Apoptose
/
Neocórtex
/
Proteínas do Tecido Nervoso
/
Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Res Dev Brain Res
Assunto da revista:
CEREBRO
/
NEUROLOGIA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos