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Development ePress online publication date 22 Oct 2003
doi: 10.1242/dev.00831
Research article: Development and disease
Embryonic atrial function is essential for mouse embryogenesis, cardiac morphogenesis and angiogenesis
Chengqun Huang,
Farah Sheikh,
Melinda Hollander,
Chengleng Cai,
David Becker,
Po-Hsien Chu,
Sylvia Evans,
and
Ju Chen*
* Author for correspondence (e-mail: juchen{at}ucsd.edu)
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.
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