E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation.
Tropomodulins are a family of proteins that cap the slow-growing end of actin filaments. Erythrocyte tropomodulin (E-Tmod) stabilizes short actin protofilaments in erythrocytes and caps longer sarcomeric actin filaments in striated muscles. We report the knockin of the beta-galactosidase gene (LacZ) under the control of the endogenous E-Tmod promoter and the knockout of E-Tmod in mouse embryonic stem cells. E-Tmod(-/-) embryos die around embryonic day 10 and exhibit a noncontractile heart tube with disorganized myofibrils and underdevelopment of the right ventricle, accumulation of mechanically weakened primitive erythroid cells in the yolk sac, and failure of primary capillary plexuses to remodel into vitelline vessels, all required to establish blood circulation between the yolk sac and the embryo proper. We propose a hemodynamic "plexus channel selection" mechanism as the basis for vitelline vascular remodeling. The defects in cardiac contractility, vitelline circulation, and hematopoiesis reflect an essential role for E-Tmod capping of the actin filaments in both assembly of cardiac sarcomeres and of the membrane skeleton in erythroid cells that is not compensated for by other proteins.
Chu
Xin
X
Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
Chen
Ju
J
Reedy
Mary C
MC
Vera
Carlos
C
Sung
K-L Paul
KL
Sung
Lanping Amy
LA
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000098:blood supply / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000235:genetics; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010641:Phenotype; D012399:Rotation; D013314:Stress, Mechanical; D051348:Tropomodulin; D015017:Yolk Sac / Q000098:blood supply / Q000502:physiology
D015415:Biomarkers; D002352:Carrier Proteins; D008840:Microfilament Proteins; C495831:Tmod1 protein, mouse; D051348:Tropomodulin