Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis.
The requirement for atrial function in developing heart is unknown. To address this question, we have generated mice deficient in atrial myosin light chain 2 (MLC2a), a major structural component of the atrial myofibrillar apparatus. Inactivation of the Mlc2a gene resulted in severely diminished atrial contraction and consequent embryonic lethality at ED10.5-11.5, demonstrating that atrial function is essential for embryogenesis. Our data also address two longstanding questions in cardiovascular development: the connection between function and form during cardiac morphogenesis, and the requirement for cardiac function during vascular development. Diminished atrial function in MLC2a-null embryos resulted in a number of consistent secondary abnormalities in both cardiac morphogenesis and angiogenesis. Our results unequivocally demonstrate that normal cardiac function is directly linked to normal morphogenic development of heart and vasculature. These data have important implications for the etiology of congenital heart disease.
Institute of Molecular Medicine and Department of Medicine, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0641, USA.
Chengqun
C
Huang
Farah
F
Sheikh
Melinda
M
Hollander
Chengleng
C
Cai
David
D
Becker
Po-Hsien
PH
Chu
Sylvia
S
Evans
Ju
J
Chen
D000818:Animals; D016275:Atrial Function / Q000502:physiology*; D015415:Biomarkers; D001808:Blood Vessels / Q000002:abnormalities / Q000033:anatomy & histology; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D018390:Gene Targeting; D005838:Genotype; D006325:Heart Atria / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development / Q000648:ultrastructure; D006339:Heart Rate; D006352:Heart Ventricles / Q000648:ultrastructure; D051379:Mice; D009024:Morphogenesis; D009200:Myocardial Contraction / Q000502:physiology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010641:Phenotype
D015415:Biomarkers; D018994:Myosin Light Chains; C107184:myosin light chain 2; D024722:Cardiac Myosins