Mechanistic Target of Rapamycin (Mtor) Is Essential for Murine Embryonic Heart Development and Growth

被引：4

作者：

Zhu, Yi ^{[1
,2
,3
]}

Pires, Karla M. P. ^{[1
,2
,5
]}

Whitehead, Kevin J. ^{[4
]}

Olsen, Curtis D. ^{[4
]}

Wayment, Benjamin ^{[4
]}

Zhang, Yi Cheng ^{[1
,2
]}

Bugger, Heiko ^{[1
,2
]}

Ilkun, Olesya ^{[1
,2
]}

Litwin, Sheldon E. ^{[4
]}

Thomas, George ^{[6
]}

Kozma, Sara C. ^{[6
]}

Abel, E. Dale ^{[1
,2
,3
]}

机构：

[1] Univ Utah, Sch Med, Div Endocrinol Metab & Diabet, Salt Lake City, UT 84112 USA

[2] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT USA

[3] Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT USA

[4] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT USA

[5] Univ Estado Rio De Janeiro, Lab Morphometry & Cardiovasc Morphol, Inst Biol, Biomed Ctr, Rio De Janeiro, Brazil

[6] Univ Cincinnati, Coll Med, Dept Internal Med, Metab Dis Inst,Div Hematol Oncol, Cincinnati, OH USA

来源：

PLOS ONE | 2013年 / 8卷 / 01期

关键词：

GENE-EXPRESSION; MAMMALIAN TARGET; CARDIAC-FUNCTION; IN-VIVO; COMPLEX; MOUSE; MUSCLE; RICTOR; PHOSPHORYLATION; PROLIFERATION;

D O I：

10.1371/journal.pone.0054221

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mechanistic target of rapamycin (Mtor) is required for embryonic inner cell mass proliferation during early development. However, Mtor expression levels are very low in the mouse heart during embryogenesis. To determine if Mtor plays a role during mouse cardiac development, cardiomyocyte specific Mtor deletion was achieved using alpha myosin heavy chain (alpha-MHC) driven Cre recombinase. Initial mosaic expression of Cre between embryonic day (E) 10.5 and E11.5 eliminated a subset of cardiomyocytes with high Cre activity by apoptosis and reduced overall cardiac proliferative capacity. The remaining cardiomyocytes proliferated and expanded normally. However loss of 50% of cardiomyocytes defined a threshold that impairs the ability of the embryonic heart to sustain the embryo's circulatory requirements. As a result 92% of embryos with cardiomyocyte Mtor deficiency died by the end of gestation. Thus Mtor is required for survival and proliferation of cardiomyocytes in the developing heart.

引用

页数：11

共 28 条

[1] Stereological and Histological Analysis of the Developing Rat Heart [J].

Altunkaynak, M. E. ;

Altunkaynak, B. Z. ;

Unal, D. ;

Yildirim, S. ;

Can, I. ;

Unal, B. .

ANATOMIA HISTOLOGIA EMBRYOLOGIA, 2011, 40 (06) :402-410

[2] Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression [J].

Belke, DD ;

Betuing, S ;

Tuttle, MJ ;

Graveleau, C ;

Young, ME ;

Pham, M ;

Zhang, DF ;

Cooksey, RC ;

McClain, DA ;

Litwin, SE ;

Taegtmeyer, H ;

Severson, D ;

Kahn, CR ;

Abel, ED .

JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (05) :629-639

[3] Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy [J].

Bentzinger, C. Florian ;

Romanino, Klaas ;

Cloetta, Dimitri ;

Lin, Shuo ;

Mascarenhas, Joseph B. ;

Oliveri, Filippo ;

Xia, Jinyu ;

Casanova, Emilio ;

Costa, Celine F. ;

Brink, Marijke ;

Zorzato, Francesco ;

Hall, Michael N. ;

Rueegg, Markus A. .

CELL METABOLISM, 2008, 8 (05) :411-424

[4] mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcriptional complex [J].

Cunningham, John T. ;

Rodgers, Joseph T. ;

Arlow, Daniel H. ;

Vazquez, Francisca ;

Mootha, Vamsi K. ;

Puigserver, Pere .

NATURE, 2007, 450 (7170) :736-U12

[5] TOR complex 2: a signaling pathway of its own [J].

Cybulski, Nadine ;

Hall, Michael N. .

TRENDS IN BIOCHEMICAL SCIENCES, 2009, 34 (12) :620-627

[6] mTOR complex 2 in adipose tissue negatively controls whole-body growth [J].

Cybulski, Nadine ;

Polak, Pazit ;

Auwerx, Johan ;

Rueegg, Markus A. ;

Hall, Michael N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (24) :9902-9907

[7] Mammalian target of rapamycin complex 1: Signalling inputs, substrates and feedback mechanisms [J].

Dunlop, E. A. ;

Tee, A. R. .

CELLULAR SIGNALLING, 2009, 21 (06) :827-835

[8] Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development [J].

Gangloff, YG ;

Mueller, M ;

Dann, SG ;

Svoboda, P ;

Sticker, M ;

Spetz, JF ;

Um, SH ;

Brown, EJ ;

Cereghini, S ;

Thomas, G ;

Kozma, SC .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (21) :9508-9516

[9] Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3 [J].

Gaussin, V ;

Van de Putte, T ;

Mishina, Y ;

Hanks, MC ;

Zwijsen, A ;

Huylebroeck, D ;

Behringer, RR ;

Schneider, MD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (05) :2878-2883

[10] FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse [J].

Hentges, KE ;

Sirry, B ;

Gingras, AC ;

Sarbassov, D ;

Sonenberg, N ;

Sabatini, D ;

Peterson, AS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13796-13801

← 1 2 3 →