Aberrant Myofibril Assembly in Tropomodulin1 Null Mice Leads to Aborted Heart Development and Embryonic Lethality
Tropomodulin1 (Tmod1) caps thin filament pointed ends in striated muscle, where it controls filament lengths by regulating actin dynamics. Here, we investigated myofibril assembly and heart development in a Tmod1 knockout mouse. In the absence of Tmod1, embryonic development appeared normal up to em...
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Published in | The Journal of cell biology Vol. 163; no. 5; pp. 1033 - 1044 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Rockefeller University Press
08.12.2003
The Rockefeller University Press |
Subjects | |
Online Access | Get full text |
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Summary: | Tropomodulin1 (Tmod1) caps thin filament pointed ends in striated muscle, where it controls filament lengths by regulating actin dynamics. Here, we investigated myofibril assembly and heart development in a Tmod1 knockout mouse. In the absence of Tmod1, embryonic development appeared normal up to embryonic day (E) 8.5. By E9.5, heart defects were evident, including aborted development of the myocardium and inability to pump, leading to embryonic lethality by E10.5. Confocal microscopy of hearts of E8-8.5 Tmod1 null embryos revealed structures resembling nascent myofibrils with continuous F-actin staining and periodic dots of α-actinin, indicating that I-Z-I complexes assembled in the absence of Tmod1. Myomesin, a thick filament component, was also assembled normally along these structures, indicating that thick filament assembly is independent of Tmod1. However, myofibrils did not become striated, and gaps in F-actin staining (H zones) were never observed. We conclude that Tmod1 is required for regulation of actin filaments lengths and myofibril maturation; this is critical for heart morphogenesis during embryonic development. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 K.L. Fritz-Six and P.R. Cox contributed equally to this work. Address correspondence to Velia M. Fowler, Department of Cell Biology, CB163, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037. Tel.: (858) 784-8277. Fax: (858) 784-8753. email: velia@scripps.edu Abbreviation used in this paper: Tmod, tropomodulin. |
ISSN: | 0021-9525 1540-8140 |
DOI: | 10.1083/jcb.200308164 |