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Part of the book series: Cardiovascular Molecular Morphogenesis ((CARDMM))

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Abstract

Cardiac muscle sarcomeres are complex structures composed of numerous proteins organized in an exquisitely precise manner. Studies using cultured myocytes combined with analysis of myofibril assembly in the developing heart in vivo have yielded a model for assembly that provides a framework for future experiments. The stage is now set for mechanistic and functional analyses in differentiating cardiac myocytes. These types of experiments will require developmental systems in which precardiac cells are targeted with function altering proteins or antibodies, or in which expression of specific myofibrillar constituents is ablated or foreign genes introduced. Explants from precardiac regions of avian embryos are accessible to experimental manipulation and may offer one avenue for approaching these questions. Mouse embryonic stem cells can be induced to differentiate into beating cardiac myocytes in culture, and this system provides another potentially powerful approach for defining the function of proteins and protein domains during myofibrillogenesis. Importantly, the rapid technologic advances in imaging techniques at the light microscopic level, including confocal, deconvolution, and two (multi-) photon microscopy, is predicted to have a significant impact on this field, allowing for the generation of three-dimensional images of the spatial relationships of myofibrillar constituents during assembly. In particular, the ability to monitor the expression and assembly of sarcomeric proteins [e.g., green fluorescent protein (GFP)-tagged] in individual differentiating cardiac myocytes in real time will allow us to address questions that cannot be answered from static images. The combination of improved imaging methods, new developmental models, and gene ablation and modification technologies promise to enable detailed analyses of the mechanisms involved in myofibril assembly including important protein interactions regulating thick and thin filament length specification, and the potential role of titin as a molecular scaffold in the assembly process.

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Gregorio, C.C., Antin, P.B. (2001). Myofibrillogenesis in the Heart. In: Tomanek, R.J., Runyan, R.B. (eds) Formation of the Heart and Its Regulation. Cardiovascular Molecular Morphogenesis. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4612-0207-3_2

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