Abstract
Mutations in the human Filamin A (FLNA) gene disrupt neuronal migration to the cerebral cortex and cause cardiovascular defects. Complete loss of Flna in mice results in embryonic lethality with severe cardiac structural defects involving ventricles, atria, and outflow tracts, as well as widespread aberrant vascular patterning. Despite these widespread developmental defects, migration and motility of many cell types does not appear to be affected. Instead, Flna-null embryos display abnormal epithelial and endothelial organization and aberrant adherens junctions in developing blood vessels, heart, brain, and other tissues. Essential roles for FLNA in intercellular junctions provide a mechanism for the diverse developmental defects seen in patients with FLNA mutations.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Brain / embryology
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Brain / metabolism
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Cell Communication*
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Cell Movement
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Cells, Cultured
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Contractile Proteins / deficiency
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Contractile Proteins / genetics
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Contractile Proteins / metabolism*
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Embryo, Mammalian / blood supply*
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Embryo, Mammalian / embryology
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Embryo, Mammalian / metabolism*
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Endothelial Cells / metabolism
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Filamins
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Heart / embryology*
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Heart Failure / genetics
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Heart Failure / metabolism
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Heart Failure / pathology
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Mice
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Mice, Transgenic
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Microfilament Proteins / deficiency
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Mutation / genetics
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Myocardium / metabolism*
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Neural Crest / cytology
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Neural Crest / embryology
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Neural Crest / metabolism
Substances
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Contractile Proteins
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Filamins
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Microfilament Proteins