%0 Journal Article %1 doi:10.1073/pnas.1703406114 %A Stopp, Sabine %A Gründl, Marco %A Fackler, Marc %A Malkmus, Jonas %A Leone, Marina %A Naumann, Ronald %A Frantz, Stefan %A Wolf, Elmar %A von Eyss, Björn %A Engel, Felix B. %A Gaubatz, Stefan %D 2017 %J Proceedings of the National Academy of Sciences %K gaubatz %N 30 %P 8029-8034 %R 10.1073/pnas.1703406114 %T Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development %U https://www.pnas.org/doi/abs/10.1073/pnas.1703406114 %V 114 %X Here, we demonstrate that mice lacking GAS2L3, a cytoskeleton-associated protein that interacts with actin filaments and tubulin, develop cardiomyopathy and heart failure after birth. During embryogenesis, cardiomyocytes rapidly divide. In the perinatal and neonatal period, cardiomyocytes withdraw from the cell cycle, binucleate, and the further increase in cardiac mass is achieved by hypertrophy. Germ-line deletion of Gas2l3 results in decreased cardiomyocyte proliferation and in cardiomyocyte hypertrophy. Embryonal cardiomyocytes from Gas2l3-deficient mice exhibit increased expression of the cell cycle inhibitor p21 and display premature binucleation of cardiomyocytes due to defects in cytokinetic abscission. Together these results suggest that GAS2L3 plays a central role in cardiomyocyte proliferation and cytokinesis during development. GAS2L3 is a recently identified cytoskeleton-associated protein that interacts with actin filaments and tubulin. The in vivo function of GAS2L3 in mammals remains unknown. Here, we show that mice deficient in GAS2L3 die shortly after birth because of heart failure. Mammalian cardiomyocytes lose the ability to proliferate shortly after birth, and further increase in cardiac mass is achieved by hypertrophy. The proliferation arrest of cardiomyocytes is accompanied by binucleation through incomplete cytokinesis. We observed that GAS2L3 deficiency leads to inhibition of cardiomyocyte proliferation and to cardiomyocyte hypertrophy during embryonic development. Cardiomyocyte-specific deletion of GAS2L3 confirmed that the phenotype results from the loss of GAS2L3 in cardiomyocytes. Cardiomyocytes from Gas2l3-deficient mice exhibit increased expression of a p53-transcriptional program including the cell cycle inhibitor p21. Furthermore, loss of GAS2L3 results in premature binucleation of cardiomyocytes accompanied by unresolved midbody structures. Together these results suggest that GAS2L3 plays a specific role in cardiomyocyte cytokinesis and proliferation during heart development.

@article{doi:10.1073/pnas.1703406114, abstract = {Here, we demonstrate that mice lacking GAS2L3, a cytoskeleton-associated protein that interacts with actin filaments and tubulin, develop cardiomyopathy and heart failure after birth. During embryogenesis, cardiomyocytes rapidly divide. In the perinatal and neonatal period, cardiomyocytes withdraw from the cell cycle, binucleate, and the further increase in cardiac mass is achieved by hypertrophy. Germ-line deletion of Gas2l3 results in decreased cardiomyocyte proliferation and in cardiomyocyte hypertrophy. Embryonal cardiomyocytes from Gas2l3-deficient mice exhibit increased expression of the cell cycle inhibitor p21 and display premature binucleation of cardiomyocytes due to defects in cytokinetic abscission. Together these results suggest that GAS2L3 plays a central role in cardiomyocyte proliferation and cytokinesis during development. GAS2L3 is a recently identified cytoskeleton-associated protein that interacts with actin filaments and tubulin. The in vivo function of GAS2L3 in mammals remains unknown. Here, we show that mice deficient in GAS2L3 die shortly after birth because of heart failure. Mammalian cardiomyocytes lose the ability to proliferate shortly after birth, and further increase in cardiac mass is achieved by hypertrophy. The proliferation arrest of cardiomyocytes is accompanied by binucleation through incomplete cytokinesis. We observed that GAS2L3 deficiency leads to inhibition of cardiomyocyte proliferation and to cardiomyocyte hypertrophy during embryonic development. Cardiomyocyte-specific deletion of GAS2L3 confirmed that the phenotype results from the loss of GAS2L3 in cardiomyocytes. Cardiomyocytes from Gas2l3-deficient mice exhibit increased expression of a p53-transcriptional program including the cell cycle inhibitor p21. Furthermore, loss of GAS2L3 results in premature binucleation of cardiomyocytes accompanied by unresolved midbody structures. Together these results suggest that GAS2L3 plays a specific role in cardiomyocyte cytokinesis and proliferation during heart development.}, added-at = {2022-03-29T22:58:25.000+0200}, author = {Stopp, Sabine and Gründl, Marco and Fackler, Marc and Malkmus, Jonas and Leone, Marina and Naumann, Ronald and Frantz, Stefan and Wolf, Elmar and von Eyss, Björn and Engel, Felix B. and Gaubatz, Stefan}, biburl = {https://www.bibsonomy.org/bibtex/2afd906f0b0f1c7492f301b8f1c23f37f/bcz-wue}, doi = {10.1073/pnas.1703406114}, eprint = {https://www.pnas.org/doi/pdf/10.1073/pnas.1703406114}, interhash = {35705b230215a1a2b1a93b9d9cca31bb}, intrahash = {afd906f0b0f1c7492f301b8f1c23f37f}, journal = {Proceedings of the National Academy of Sciences}, keywords = {gaubatz}, number = 30, pages = {8029-8034}, timestamp = {2022-03-29T22:58:25.000+0200}, title = {Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development}, url = {https://www.pnas.org/doi/abs/10.1073/pnas.1703406114}, volume = 114, year = 2017 }