Genetically encoded tension heterogeneity sculpts cardiac trabeculation
Jinxiu Liang1,2,3, Peijun Jiang1,2,3, Shuaifang Yan4
1Department of Cardiology, Center for Genetic Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Science Advances
|March 7, 2025
Summary
Cardiomyocyte fate is determined by erbb2 signaling, which drives cell delamination for trabeculae formation. Neighboring cells then suppress erbb2 to maintain the compact layer, orchestrating heart development.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Cellular Signaling
Background:
- The developing heart wall comprises a single cardiomyocyte layer, with cells differentiating into either trabecular or compact layers.
- The precise molecular mechanisms dictating cardiomyocyte fate and subsequent layer formation are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms governing cardiomyocyte fate decisions during myocardial wall development.
- To investigate the role of erbb2 signaling in the formation of cardiac trabeculae and the compact layer.
Main Methods:
- Single-cell RNA sequencing to analyze gene expression.
- Genetically encoded biosensors to track signaling pathways.
- In toto live imaging to observe cellular dynamics during heart development.
Main Results:
- Intrinsic variations in erbb2 expression correlate with the decision for cardiomyocytes to form trabeculae.
- erbb2 signaling activates PI3K and recruits the Arp2/3 complex, promoting actomyosin network polarization and cell delamination.
- Notch signaling in adjacent cardiomyocytes suppresses erbb2 expression in newly formed trabeculae, reducing cell tension and confining them to the compact layer.
Conclusions:
- A coordinated genetic and cellular interplay, involving erbb2 and Notch signaling, dictates cardiomyocyte fate.
- This mechanism is crucial for the precise pattern formation of the myocardial wall during embryonic development.
Related Concept Videos
01:13Structure of Cardiac Muscles
Cardiac muscle, or myocardium, is a specialized type of muscle found exclusively in the heart. Its unique structural and functional characteristics enable the heart to perform its vital role of pumping blood throughout the body continuously and rhythmically. The cardiac muscle cells, or cardiomyocytes, possess an endomysium and perimysium but do not have an epimysium.
Compared to skeletal muscles, cardiac muscle cells are small and mostly have a single nucleus. Additionally, they are usually...
Compared to skeletal muscles, cardiac muscle cells are small and mostly have a single nucleus. Additionally, they are usually...
01:27Specialized Characteristics of Cardiac Muscles
The primary role of cardiac muscles is to propel blood throughout the cardiovascular system. The cardiac muscle cells, or cardiomyocytes, exhibit specialized characteristics that allow them to perform this function.
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...