What can zebrafish teach us about developmental biology?

The organs of one aquatic organism may hold clues for human development. By studying the zebrafish, researchers in Kansas City, Missouri are making new discoveries in developmental biology.

TRANSCRIPT

The organs of one aquatic organism may hold clues for human development.

By studying the zebrafish, the researchers are making new discoveries in developmental biology.

Here's the story.

The Stowers Institute for Medical Research in Kansas City has been described as cutting-edge technology integrated with broad-based expertise to ask sophisticated questions.

The research undertaken here falls in the category of basic or fundamental, which often leads to the question, what exactly does that mean?

I like to think of basic research as the engine for discovery.

You need to make discoveries.

And once those discoveries are made, they can serve as the basis or the foundation as a process so that those ideas can be translated, developed, and then eventually applied for human health or medicine.

And zebrafish are playing a role in that process in Tatjana Piotrowski's Stowers laboratory.

These familiar-looking members of the minnow family are used as model organisms for studying developmental biology.

Basically, how cells form tissues and tissues become organs.

A zebrafish embryo grows outside its mother and remains transparent, so its developmental processes can be easily viewed.

It's quite fascinating to look at embryos under a microscope because you can actually see single cells move, interact with their environment.

You can see how organs form, whether the brain forms normally, whether the heart beats normally.

Tatjana and her team are especially interested in investigating a sensory system called the lateral line that's found in all aquatic vertebrates.

It's important to the schooling behavior of fish and allows them to detect prey or potential predators.

The lateral line gets its name from the way multiple copies of its main sensory organ, the neuromast, are dotted along a fish's body and around the eyes.

And each sense organ possesses receptor cells, which are called hair cells because they have cilia sticking out into the environment, which look like little hairs, and as water flows across these cilia, it actually sends a signal to the brain, and so that's how the animal measures the water movement.

The lateral line gradually develops from a group of around 100 cells called the primordium.

The primordium first forms behind the fish's ear.

It then begins migrating toward the tail tip.

It's divided into the leading edge and the trailing edge.

It raises, really, a lot of interesting questions.

So, for example, how does a group of cells know which direction to migrate?

Do they just follow the cell in the tip, or does each cell know which direction to go?

There are several theories about how small cell clusters that look like rosettes eventually become neuromasts.

And testing requires a whole lot of fish.

Adult zebrafish will lay up to 200 eggs per week.

And this allows us to do large-scale genetic mutagenesis screens.

What this means is, we are disrupting gene function randomly by -- with mutagens that we can apply on the adult fish.

So, we can disrupt genes, and then we look at the life embryo, and now you see, okay, these cells are not behaving anymore like they were supposed to, and then this way, it gives us a tool to identify what these genes are normally doing.

Okay, so, why is the Piotrowski lab focusing on a sensory organ in fish?

Well, because neuromast hair cells, by which fish sense water movement, are actually very similar to those found in the human inner ear.

However, our inner-ear hair cells turn sound vibration into electrical activity, which nerve fibers transmit to our brain, allowing us to hear.

If you disrupt particular genes in the zebrafish electrolyte hair cells, they stop functioning, and the same genes cause deafness in humans, for example.

A zebrafish's hair cells are just as susceptible as ours to damage and death, from overexposure to noise, or the wear and tear of aging.

But unlike us, they have a secret weapon.

It's called regeneration, in which new hair cells regularly replace any that have been injured or killed.

Once we understand how regeneration happens in a fish, we will then be able to also compare it to a mouse and see where this process is blocked in a mouse or even in other animals such as humans.

Way I like to think about it is, the model system is a way of learning how things are put together, to understand cues and instructions, and then you can compare and contrast those.

They're often instructions that are used primarily in a fish that also play a role in a human they weren't aware of.

But if you don't make the discoveries, you don't have a way of moving forward.

And, unfortunately, sometimes 90% of what we do doesn't work, but the 10% that do can shape the future of mankind.