title: Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis.
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.
authors.affiliation: Division of Genetics and Department of Cardiology, Children's Hospital Boston, Boston, MA 02215, USA.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Feng
authors.forename: Ming Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Ivan P
authors.initials: IP
authors.lastname: Moskowitz
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Mendonza
authors.forename: Luis
authors.initials: L
authors.lastname: Vidali
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000098:blood supply* / Q000196:embryology / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D064448:Filamins; D006321:Heart / Q000196:embryology*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins