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Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart

Rutland, Catrin S.; Polo-Parada, Luis; Ehler, Elisabeth; Alibhai, Aziza; Thorpe, Aaran; Suren, Suganthi; Emes, Richard D.; Patel, Bhakti; Loughna, Siobhan

Authors

Catrin S. Rutland

Luis Polo-Parada

Elisabeth Ehler

Aziza Alibhai

Aaran Thorpe

Suganthi Suren

Richard D. Emes

Bhakti Patel

Siobhan Loughna



Abstract

The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy.

Journal Article Type Article
Publication Date Sep 15, 2011
Journal Development
Print ISSN 0950-1991
Electronic ISSN 1477-9129
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 138
Issue 18
APA6 Citation Rutland, C. S., Polo-Parada, L., Ehler, E., Alibhai, A., Thorpe, A., Suren, S., …Loughna, S. (2011). Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart. Development, 138(18), https://doi.org/10.1242/dev.059063
DOI https://doi.org/10.1242/dev.059063
Publisher URL http://dev.biologists.org/content/138/18/3955.full
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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