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Advancements in Heart Development Research Using MorphoHeart

MorphoHeart enhances the study of heart growth and defects in zebrafish embryos.

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MorphoHeart: TransformingMorphoHeart: TransformingHeart Researchdevelopment analysis in zebrafish.New tool revolutionizes heart
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The heart is a complex organ that develops through several stages to take its final form. Early in development, it starts as a simple tube. This tube then bends and loops to form the different parts of the heart as we know it. This process is crucial because if something goes wrong at this stage, it can lead to serious problems with how the heart works later on.

During the early stages, the heart has an outer layer called the Myocardium and an inner layer called the endocardium. These layers are important for different heart functions. The myocardial layer is responsible for heart contractions, while the endocardium lines the chambers of the heart.

As the heart develops, it goes through changes that prepare it for its future function. The shape of the heart becomes more complex as it forms chambers and valves. These structures are needed for the heart to properly pump blood throughout the body. Any issues during these early stages can lead to heart defects, affecting its shape and how it operates.

The Role of Extracellular Matrix (ECM)

The extracellular matrix (ECM) is a network of proteins and other molecules found outside of cells. It provides support and structure to tissues, including the heart. The ECM sends signals to heart cells, helping them grow and develop properly. During the early stages of heart development, the ECM is rich in specific molecules that help the transitioning heart form its shape.

One of these key molecules is Hyaluronic Acid (HA), which helps the ECM take in water. This swelling can create pressure in the heart structure, which is crucial for forming the heart's different parts. If the ECM doesn’t work correctly, it can lead to problems in how the heart develops.

Limitations in Current Research

Researchers currently face challenges when studying how the heart forms and changes shape. Most research has been done by analyzing fixed samples, which can shrink and change the actual structures being studied. This can make it difficult to see how the heart is truly developing. Some studies have tried to look at live samples, but this is challenging because it’s hard to observe embryos that usually develop inside their mother.

Zebrafish are a great model for studying heart development. Their embryos are transparent, which allows researchers to see the heart as it develops without interference. This species also has well-known genetic pathways for heart disease, making it a valuable tool for study.

However, much of the analysis that has been done on zebrafish hearts has been limited to simple measurements that don’t capture the full complexity of heart structures. More sophisticated methods and tools are needed to analyze the heart accurately.

Introducing morhoHeart

To address these limitations, researchers have developed a new tool called morphoHeart. This software allows for detailed analysis and visualization of the developing heart in live zebrafish embryos. It can analyze multiple tissue layers, including the ECM, and provide various measurements about heart structure.

MorphoHeart is designed to be accessible for researchers with different skill levels. It can handle complex tissue shapes and provide metrics on tissue volume, thickness, and other important characteristics. It also allows users to separate and examine different regions of the heart, which is important for understanding how each part develops.

Analyzing Heart Morphology

Using morphoHeart, researchers can collect data on how the heart changes over time. For example, they can analyze the heart during crucial stages of development, such as looping and ballooning. Looping refers to the way the heart bends into its proper shape, while ballooning is when the heart chambers begin to form.

By capturing images of the heart at different stages, researchers can create 3D models that show how the heart is growing and changing. These models help visualize the size and shape of the heart, allowing for accurate comparisons between the heart’s various parts throughout development.

Changes in Heart Size and Shape

During heart development, both size and shape are important. As the heart tubes loop and balloon, they grow larger, increasing their ability to pump blood. Early analysis shows that after the initial looping, the heart grows significantly. For example, between certain stages of development, the volume of both the myocardium and endocardium increases. However, after reaching a peak, the heart may start to shrink, particularly in the atrium, while the ventricle keeps a more stable volume.

These changes in size are important for how the heart functions. Researchers can look at these dynamics to understand how heart defects might arise and how various heart conditions could be treated.

Regional Dynamics in Heart Development

The research reveals that different parts of the heart can experience changes at different rates. For instance, the atria and ventricles show distinct pathways of growth and shrinkage. While the atria might reduce in size after initial development, the ventricles may continue to grow or maintain their size.

Such regional differences in growth highlight how complicated the heart-building process is. By studying these specific parts, researchers can gain insights into how these structures work together to form a fully functional heart.

Importance of Cardiac ECM

The cardiac extracellular matrix (ECM) also undergoes changes throughout heart development. Researchers found that the ECM grows and shrinks in volume, often in sync with the heart chambers.

The ECM has a crucial role in providing structural support and signaling for heart cells. It can be regionalized, which means that different areas of the heart have distinct ECM characteristics. For instance, the ECM may be thicker in the atria compared to the ventricles, which can influence how each chamber develops.

Identifying these differences can make it easier to understand how problems in ECM formation could lead to heart defects. The matrix helps maintain the structure of the heart while allowing those tissues to grow and change shape.

Insights from Mutant Studies

Researchers also studied Mutants to see how changes in genes affect heart development. For instance, they examined mutants lacking a specific ECM protein called Hapln1a. These mutants showed significant changes in heart size and shape compared to normal zebrafish.

In hapln1a mutants, the atrium fails to expand correctly, impacting overall heart size. Observing these differences helps uncover the role of the ECM in heart development. The findings suggest that Hapln1a is important for promoting healthy growth and structure in the heart.

Conclusion: The Future of Heart Research

MorphoHeart is paving the way for new discoveries in heart research. By enabling detailed analysis of heart shape, size, and the ECM, it provides vital information for understanding heart development. This tool can help researchers study how heart defects occur and explore ways to prevent or treat these conditions.

By examining heart development in zebrafish, scientists can generate insights that might translate into improved treatments for heart diseases in humans. The ability to analyze complex structures and their changes over time will undoubtedly enhance our understanding of heart morphogenesis and how to address congenital heart defects.

Original Source

Title: morphoHeart: a novel quantitative tool to perform integrated 3D morphometric analyses of heart and ECM morphology during embryonic development

Abstract: Heart development involves the complex structural remodelling of a linear heart tube into an asymmetrically looped and ballooned organ. Previous studies have associated regional expansion of extracellular matrix (ECM) space with tissue morphogenesis during development. We have developed morphoHeart, an 3D image tissue segmentation and morphometry software which delivers the first integrated 3D visualisation and multiparametric analysis of both heart and ECM morphology in live embryos. morphoHeart reveals that the ECM undergoes regional dynamic expansion and reduction during cardiac development, concomitant with chamber-specific morphological maturation. We use morphoHeart to demonstrate that regionalised ECM expansion driven by the ECM crosslinker Hapln1a promotes atrial lumen expansion during heart development. Finally, we have developed a GUI that allows the morphometric analysis tools of morphoHeart to be applied to z-stack images of any fluorescently-labelled tissue.

Authors: Emily S Noël, J. Sanchez-Posada, E. S. Noël

Last Update: 2024-02-21 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.02.19.580991

Source PDF: https://www.biorxiv.org/content/10.1101/2024.02.19.580991.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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