Abstract

To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (ANkx/ANkx) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 ANkx/ANkx mice) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from the original embryonic stem cell line was tested. This second line also develops SCC indistinguishable from the first (15/15 ANkx/ANkx mice). In ANkx/ANkx mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL004218-25
Application #
9157333
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Baird, Michelle A; Billington, Neil; Wang, Aibing et al. (2017) Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells. Mol Biol Cell 28:240-251
Naydenov, Nayden G; Feygin, Alex; Wang, Dongdong et al. (2016) Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and Plays a Protective Role During Experimental Colitis. Sci Rep 6:24161
Conti, Mary Anne; Saleh, Anthony D; Brinster, Lauren R et al. (2015) Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma. Sci Rep 5:14068
Recuenco, Mariam C; Ohmori, Tomoko; Tanigawa, Shunsuke et al. (2015) Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons. J Am Soc Nephrol 26:1081-91
Kwan, Raymond; Chen, Lu; Looi, Koksun et al. (2015) PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Hepatology 62:1858-69
Chandrasekar, Indra; Goeckeler, Zoe M; Turney, Stephen G et al. (2014) Nonmuscle myosin II is a critical regulator of clathrin-mediated endocytosis. Traffic 15:418-32
Crish, James; Conti, Mary Anne; Sakai, Takao et al. (2013) Keratin 5-Cre-driven excision of nonmuscle myosin IIA in early embryo trophectoderm leads to placenta defects and embryonic lethality. Dev Biol 382:136-48
Ebrahim, Seham; Fujita, Tomoki; Millis, Bryan A et al. (2013) NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry. Curr Biol 23:731-6
Doyle, Andrew D; Kutys, Matthew L; Conti, Mary Anne et al. (2012) Micro-environmental control of cell migration--myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics. J Cell Sci 125:2244-56
Zhang, Yingfan; Conti, Mary Anne; Malide, Daniela et al. (2012) Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood 119:238-50

Showing the most recent 10 out of 23 publications