New genetic discovery improves understanding of congenital heart disease

A new study led by the Masonic Medical Research Institute, published in the journal Cells, shows for the first time that a specific gene called VGLL4 is required for embryonic development but dispensable for myocardial growth. This fact was previously unknown, and with this discovery, medical researchers now have useful new information about the development of heart cells that will aid in our understanding of congenital heart defects and heart failure.

Why it matters: Congenital heart disease is a leading cause of pediatric morbidity and mortality, making it important to unravel the molecular mechanisms that control heart development. Cardiovascular development has become a crucial element in understanding congenital heart disease, and the more we know about it, the better we can treat heart defects.

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Context: Vestigial like family member 4 is a protein encoded by the VGLL4 gene; This is a transcription cofactor of the VGLL family found in many organs and tissues. VGLL4 has been identified as a tumor suppressor and has been extensively explored in cancer studies.

Study Summary: To understand VGLL4 function in the heart, the authors generated two VGLL4 loss-of-function mouse lines: a germline VGLL4 depletion allele and a cardiomyocyte-specific VGLL4 depletion allele. Analysis of the embryos revealed that VGLL4 knockout embryos had reduced body size, malformed tricuspid valves, but normal myocardium and cardiac function. Read the full article cellslinked here:

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What’s new here: This is a newly discovered feature about VGLL4; This protein is required for embryonic development, but this function is independent and isolated from the growth of the heart’s myocardial wall.

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Team Authors: Caroline Sheldon, Aaron Farley, Qing Ma, William Pu, and Zhiqiang Lin. dr Zhiqiang Lin, who is a senior researcher at the Masonic Medical Research Institute, led the team. The research team includes colleagues from Harvard Stem Cell Institute and Boston Children’s Hospital. dr Lin co-authored a previous study on VGLL4 in 2016, also with Dr. Pu and Dr. mom


Masonic Medical Research Institute

Magazine reference:

Sheldon, C. et al. (2022) VGLL4 depletion causes perinatal lethality without affecting myocardial development. cells.

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