title: Knockdown of alpha myosin heavy chain disrupts the cytoskeleton and leads to multiple defects during chick cardiogenesis.
abstract: Atrial septal defects are a common congenital heart defect in humans. Although mutations in different genes are now frequently being described, little is known about the processes and mechanisms behind the early stages of atrial septal development. By utilizing morpholino-induced knockdown in the chick we have analysed the role of alpha myosin heavy chain during early cardiogenesis in a temporal manner. Upon knockdown of alpha myosin heavy chain, three different phenotypes of the atrial septum were observed: (1) the atrial septum failed to initiate, (2) the septum was initiated but was growth restricted, or (3) incorrect specification occurred resulting in multiple septa forming. In addition, at a lower frequency, decreased alpha myosin heavy chain was found to give rise to an abnormally looped heart or an enlarged heart. Staining of the actin cytoskeleton indicated that many of the myofibrils in the knockdown hearts were not as mature as those observed in the controls, suggesting a mechanism for the defects seen. Therefore, these data suggest a role for alpha myosin heavy chain in modelling of the early heart and the range of defects to the atrial septum suggest roles in its initiation, specification and growth during development.
authors.affiliation: University of Nottingham, Queens Medical Centre, UK.
authors.forename: Catrin
authors.initials: C
authors.lastname: Rutland
authors.forename: Louise
authors.initials: L
authors.lastname: Warner
authors.forename: Aaran
authors.initials: A
authors.lastname: Thorpe
authors.forename: Aziza
authors.initials: A
authors.lastname: Alibhai
authors.forename: Thelma
authors.initials: T
authors.lastname: Robinson
authors.forename: Barry
authors.initials: B
authors.lastname: Shaw
authors.forename: Robert
authors.initials: R
authors.lastname: Layfield
authors.forename: J David
authors.initials: JD
authors.lastname: Brook
authors.forename: Siobhan
authors.initials: S
authors.lastname: Loughna
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D054087:Atrial Septum / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D006332:Cardiomegaly / Q000196:embryology / Q000473:pathology; D002642:Chick Embryo; D003599:Cytoskeleton / Q000473:pathology*; D047108:Embryonic Development; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology*; D010641:Phenotype; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D024723:Ventricular Myosins