Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality

Kimberly L. Fritz-Six, Patrick R. Cox, Robert S. Fischer, Bisong Xu, Carol Gregorio, Huda Y. Zoghbi, Velia M. Fowler

Research output: Contribution to journalArticle

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Abstract

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 filament lengths and myofibril maturation; this is critical for heart morphogenesis during embryonic development.

Original languageEnglish (US)
Pages (from-to)1033-1044
Number of pages12
JournalJournal of Cell Biology
Volume163
Issue number5
DOIs
StatePublished - Dec 8 2003

Fingerprint

Myofibrils
Embryonic Development
Actins
Connectin
Staining and Labeling
Actinin
Striated Muscle
Actin Cytoskeleton
Morphogenesis
Knockout Mice
Confocal Microscopy
Myocardium
Embryonic Structures

Keywords

  • Actin
  • Cardiac muscle
  • Sarcomere
  • Tropomodulin
  • Tropomyosin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality. / Fritz-Six, Kimberly L.; Cox, Patrick R.; Fischer, Robert S.; Xu, Bisong; Gregorio, Carol; Zoghbi, Huda Y.; Fowler, Velia M.

In: Journal of Cell Biology, Vol. 163, No. 5, 08.12.2003, p. 1033-1044.

Research output: Contribution to journalArticle

Fritz-Six, Kimberly L. ; Cox, Patrick R. ; Fischer, Robert S. ; Xu, Bisong ; Gregorio, Carol ; Zoghbi, Huda Y. ; Fowler, Velia M. / Aberrant myofibril assembly in tropomodulin1 null mice leads to aborted heart development and embryonic lethality. In: Journal of Cell Biology. 2003 ; Vol. 163, No. 5. pp. 1033-1044.
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