Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development
Congenital heart disease is one of the leading causes of pediatric morbidity and mortality, thus highlighting the importance of deciphering the molecular mechanisms that control heart development. As the terminal transcriptional effectors of the Hippo–YAP pathway, YAP and TEAD1 form a transcriptiona...
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MDPI AG
2022-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2832 |
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| author | Caroline Sheldon Aaron Farley Qing Ma William T. Pu Zhiqiang Lin |
| author_facet | Caroline Sheldon Aaron Farley Qing Ma William T. Pu Zhiqiang Lin |
| author_sort | Caroline Sheldon |
| collection | DOAJ |
| description | Congenital heart disease is one of the leading causes of pediatric morbidity and mortality, thus highlighting the importance of deciphering the molecular mechanisms that control heart development. As the terminal transcriptional effectors of the Hippo–YAP pathway, YAP and TEAD1 form a transcriptional complex that regulates the target gene expression and depletes either of these two genes in cardiomyocytes, thus resulting in cardiac hypoplasia. Vestigial-like 4 (VGLL4) is a transcriptional co-factor that interacts with TEAD and suppresses the YAP/TEAD complex by competing against YAP for TEAD binding. To understand the VGLL4 function in the heart, we generated two VGLL4 loss-of-function mouse lines: a germline <i>Vgll4</i> depletion allele and a cardiomyocyte-specific <i>Vgll4</i> depletion allele. The whole-body deletion of <i>Vgll4</i> caused defective embryo development and perinatal lethality. The analysis of the embryos at day 16.5 revealed that <i>Vgll4</i> knockout embryos had reduced body size, malformed tricuspid valves, and normal myocardium. Few whole-body <i>Vgll4</i> knockout pups could survive up to 10 days, and none of them showed body weight gain. In contrast to the whole-body <i>Vgll4</i> knockout mutants, cardiomyocyte-specific <i>Vgll4</i> knockout mice had no noticeable heart growth defects and had normal heart function. In summary, our data suggest that VGLL4 is required for embryo development but dispensable for myocardial growth. |
| first_indexed | 2024-03-10T00:27:05Z |
| format | Article |
| id | doaj.art-d8954f674a994b1b9013fd6fdcada5b9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:27:05Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-d8954f674a994b1b9013fd6fdcada5b92023-11-23T15:32:59ZengMDPI AGCells2073-44092022-09-011118283210.3390/cells11182832Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial DevelopmentCaroline Sheldon0Aaron Farley1Qing Ma2William T. Pu3Zhiqiang Lin4Masonic Medical Research Institute, 2150 Bleecker St., Utica, NY 13501, USAMasonic Medical Research Institute, 2150 Bleecker St., Utica, NY 13501, USADepartment of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USADepartment of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USAMasonic Medical Research Institute, 2150 Bleecker St., Utica, NY 13501, USACongenital heart disease is one of the leading causes of pediatric morbidity and mortality, thus highlighting the importance of deciphering the molecular mechanisms that control heart development. As the terminal transcriptional effectors of the Hippo–YAP pathway, YAP and TEAD1 form a transcriptional complex that regulates the target gene expression and depletes either of these two genes in cardiomyocytes, thus resulting in cardiac hypoplasia. Vestigial-like 4 (VGLL4) is a transcriptional co-factor that interacts with TEAD and suppresses the YAP/TEAD complex by competing against YAP for TEAD binding. To understand the VGLL4 function in the heart, we generated two VGLL4 loss-of-function mouse lines: a germline <i>Vgll4</i> depletion allele and a cardiomyocyte-specific <i>Vgll4</i> depletion allele. The whole-body deletion of <i>Vgll4</i> caused defective embryo development and perinatal lethality. The analysis of the embryos at day 16.5 revealed that <i>Vgll4</i> knockout embryos had reduced body size, malformed tricuspid valves, and normal myocardium. Few whole-body <i>Vgll4</i> knockout pups could survive up to 10 days, and none of them showed body weight gain. In contrast to the whole-body <i>Vgll4</i> knockout mutants, cardiomyocyte-specific <i>Vgll4</i> knockout mice had no noticeable heart growth defects and had normal heart function. In summary, our data suggest that VGLL4 is required for embryo development but dispensable for myocardial growth.https://www.mdpi.com/2073-4409/11/18/2832Vestigial-like 4tandem Tondu domains (TDUs)cardiomyocytemyocardiumdevelopment |
| spellingShingle | Caroline Sheldon Aaron Farley Qing Ma William T. Pu Zhiqiang Lin Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development Cells Vestigial-like 4 tandem Tondu domains (TDUs) cardiomyocyte myocardium development |
| title | Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development |
| title_full | Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development |
| title_fullStr | Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development |
| title_full_unstemmed | Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development |
| title_short | Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development |
| title_sort | depletion of vgll4 causes perinatal lethality without affecting myocardial development |
| topic | Vestigial-like 4 tandem Tondu domains (TDUs) cardiomyocyte myocardium development |
| url | https://www.mdpi.com/2073-4409/11/18/2832 |
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