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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2004-10-28
pubmed:abstractText
In the developing neocortex, most excitatory neurons are supplied and arranged through radial migration. Because neurons show global morphological changes and complicated behavior during that migration, precise regulation of cell shape and polarity is essential for proper migration and correct neocortical formation; however, how cell shape and polarity are regulated in migrating neuron remains elusive. We show here that Filamin A, a well known actin-binding protein, determines the shape of neocortical neurons during radial migration in vivo. Dysfunction of Filamin A, caused by a mutant Filamin A expression, prevents cells from acquiring consistent polarity toward specific direction and decreases motility in the subventricular and intermediate zones. In contrast, Filamin A overexpression, achieved by a short interfering RNA for Filamin A-interacting protein that induces Filamin A degradation (FILIP), promotes the development and maintenance of a bipolar shape also in the subventricular and intermediate zones. These results suggest that the amount of Filamin A helps migrating neurons determine their mode of migration, multipolar or bipolar, before entering the cortical plate and that FILIP is responsible, at least in part, for Filamin A content. In addition, our results also give a possible clue to understanding the pathogenesis of human malformation periventricular heterotopia, which is caused by various "loss-of-function" mutations in the filamin A gene.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9648-57
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Filamin A and FILIP (Filamin A-Interacting Protein) regulate cell polarity and motility in neocortical subventricular and intermediate zones during radial migration.
pubmed:affiliation
Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Matsuoka, Fukui 910-1193, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't