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Zebrafish Research Sheds Light on Neural Tube Defects

Zebrafish studies reveal new insights into neural tube defects and their formation.

Jacalyn MacGowan, Mara Cardenas, Margot Kossmann Williams

― 5 min read


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Neural Tube Defects (NTDs) are serious birth problems that happen when the neural tube, which develops into the brain and spinal cord, does not close completely. This can lead to conditions like spina bifida, where the spinal cord doesn’t close fully, or anencephaly, where parts of the brain are missing. Such defects can happen in about 1 in 1,000 births in the United States, and the numbers can be even higher in other countries.

How Do NTDs Form?

The neural tube is essentially a sheet of cells that folds into a tube during early development. If this folding process goes wrong, the tube may remain open or only partially close. This can happen for several reasons, such as genetic factors, lack of certain vitamins like folic acid, or environmental influences.

Why Study Zebrafish?

Researchers often turn to zebrafish as a model organism for studying NTDs. These little fish have transparent embryos, which allow scientists to see developmental processes in real-time. Plus, they breed quickly, meaning scientists can conduct experiments and gather data without having to wait too long.

Key Findings in Zebrafish Research

Primary Neurulation in Zebrafish

Primary neurulation is the process by which the neural tube forms, and it has been well studied in several animals, including zebrafish. Interestingly, the way zebrafish form their neural tube is a bit different than in mammals. Instead of closing like a zipper, zebrafish use a method that some scientists think resembles a second type of neurulation.

Conservation of Mechanisms

Despite their differences, many parts of neural tube formation are the same across species. For example, both zebrafish and other vertebrates, like mice or chickens, utilize a process called convergent extension (CE), where the cells of the neural plate stretch and narrow to form the tube. This is a bit like pulling on the ends of a piece of dough to make it longer and thinner.

The Role of Vangl2 in Neurulation

Vangl2 is a gene that is crucial during this folding process. When researchers disrupted the function of this gene in zebrafish, they noticed some concerning changes. Instead of the neural folds smoothly fusing together, they saw various weird openings, kind of like an unfinished puzzle where some pieces refuse to fit!

Abnormal Fusion Patterns

In zebrafish without Vangl2, the neural folds tended to "button up" at multiple points instead of zipping together properly. Think of it like trying to zip up a jacket that has several buttons instead of just one zipper! This means that the neural tube wasn’t closing correctly, leading to a bigger risk of NTDs.

Live Imaging Techniques

To study these processes, scientists used a technique called live imaging, which allows them to watch the development of zebrafish embryos over time. By tagging certain proteins with fluorescent markers, they could see how cells behaved during key stages of development. It’s like watching a science fiction movie where the cells are the stars!

Observing the Fusion Process

When scientists looked at how the neural folds came together in live embryos, they found some surprises. There was a distinct pattern of zippering at the back of the head and down the spine. Notably, the posterior part of the neural tube often closed before the anterior part, which is a reversal of what happens in other animals.

The Importance of Myosin

Myosin is a protein that plays a vital role in making cells change shape. During the formation of the neural tube, myosin helps cells squeeze together at the middle, elevating the neural folds. Think of it as the little muscle that helps dough rise when making a cake!

Myosin and Neural Tube Closure

The zebrafish embryos without Vangl2 showed abnormal myosin behavior. Instead of a smooth movement, the neural folds had trouble coming together, leading to bigger gaps. It was almost like having a crew of clumsy chefs trying to bake a cake but failing to keep the batter contained!

Insights from Fixed Embryos

Besides live imaging, researchers utilized fixed embryos to study the structure of the neural tube at various stages. They stained specific proteins to see how the neural tube was shaping up. And oh boy, the results were telling!

Widened Neural Plates

In embryos lacking Vangl2, researchers observed widened neural plates and openings that shouldn’t be there. It’s kind of like finding a split in a road where it’s supposed to be just one smooth way. This supports the idea that Vangl2 is crucial for proper neural tube formation.

Delay in Pineal Development

A particular structure called the pineal gland, responsible for producing a hormone that helps regulate sleep, was also impacted in these embryos. Researchers found that in the absence of Vangl2, the pineal gland could appear elongated or split, which is something you wouldn't want to see when going in for your regular sleep checkup!

How Do These Findings Help Us?

These insights are significant because they give researchers a clearer picture of how NTDs can develop. By understanding zebrafish development better, scientists can identify potential treatments or preventive measures for these congenital anomalies in humans.

A New Model for Research

Many scientists are starting to see zebrafish as a great model for understanding NTDs. The ability to observe early developmental windows and the potential to manipulate genes means that researchers can study how specific changes can lead to defects. It’s like being able to play a vivid video game where every action reveals new secrets!

Conclusion

Neural tube defects present a serious challenge, but studies using zebrafish are illuminating the path toward better understanding and potentially tackling these issues. By examining the processes that lead to NTDs in these little fish, scientists gain key insights that could one day save lives.

So the next time you see a zebrafish swimming around, remember there’s a whole lot of science happening beneath its shiny scales, working to ensure that future generations can swim freely without worries! 🐠

Original Source

Title: Fold-and-fuse neurulation in zebrafish requires Vangl2

Abstract: Shaping of the future brain and spinal cord during neurulation is an essential component of early vertebrate development. In amniote embryos, primary neurulation occurs through a "fold-and-fuse" mechanism by which the edges of the neural plate fuse into the hollow neural tube. Failure of neural fold fusion results in neural tube defects (NTDs), which are among the most devastating and common congenital anomalies worldwide. Unlike amniotes, the zebrafish neural tube develops largely via formation of a solid neural keel that later cavitates to form a midline lumen. Although many aspects of primary neurulation are conserved in zebrafish, including neural fold zippering, it was not clear how well these events resemble analogous processes in amniote embryos. Here, we demonstrate that despite outward differences, zebrafish anterior neurulation closely resembles that of mammals. For the first time in zebrafish embryos, we directly observe enclosure of a lumen by the bilateral neural folds, which fuse by zippering between at least two distinct closure sites. Both the apical constriction that elevates the neural folds and the zippering that fuses them coincide with apical Myosin enrichment. We further show that embryos lacking vangl2, a core planar cell polarity and NTD risk gene, exhibit delayed and abnormal neural fold fusion that fails to enclose a lumen. These defects can also be observed in fixed embryos, enabling their detection without live imaging. Together, our data provide direct evidence for fold-and-fuse neurulation in zebrafish and its disruption upon loss of an NTD risk gene, highlighting the deep conservation of primary neurulation across vertebrates. HighlightsO_LIThe anterior neural tube of zebrafish undergoes "fold-and-fuse" neurulation to enclose a lumen, highlighting conservation of primary neurulation mechanisms across vertebrates. C_LIO_LIAnterior neural tube closure is delayed and abnormal in zebrafish embryos lacking the planar cell polarity gene vangl2, occurring by excessive "buttoning" rather than smooth "zippering" and failing to enclose a lumen. C_LIO_LINeural tube defects (NTDs) are visible in fixed vangl2 deficient embryos, enabling simple assessment of neural tube phenotypes with potential utility in screening NTD risk genes. C_LI

Authors: Jacalyn MacGowan, Mara Cardenas, Margot Kossmann Williams

Last Update: 2024-12-02 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2023.11.09.566412

Source PDF: https://www.biorxiv.org/content/10.1101/2023.11.09.566412.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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