Scoliosis is an abnormal curvature of the spine that can cause issues with breathing, back problems and can even lead to noticeable changes such as uneven shoulders and waist. While many cases tend to be diagnosed in adolescence, doctors still have little knowledge of what causes this condition. Now, new research involving zebrafish has shed some light on the origins of scoliosis. Beth Bearce is a post-doctoral research fellow with the University of Oregon’s Grime’s Lab. They join us to share what they learned and the broader implications of the research.
This transcript was created by a computer and edited by a volunteer.
Dave Miller: From the Gert Boyle Studio at OPB, this is Think Out Loud. I’m Dave Miller. We turn now to new insights into scoliosis. That’s when an abnormal curvature of the spine can give people back problems or create issues with breathing. The new insights didn’t come from humans though. They’ve come from zebrafish. Beth Bearce is a cell biologist and a postdoctoral research fellow at the University of Oregon. They join us now to talk about this research. Beth Bearce, welcome.
Beth Bearce: Hello, it’s great to be here.
Miller: Thanks for joining us. In general, what makes studying scoliosis challenging?
Bearce: That’s a great question. So scoliosis, what we’re interested in really, or the type of scoliosis that we generally study is one called adolescent idiopathic scoliosis. Idiopathic essentially means, at its core, that we have no idea of the genetic and environmental factors that go into the ideology of this disease. So we don’t know what causes scoliosis. We know it typically arises during juvenile growth. So you have a growth spurt in your teenage years and start developing spinal curvatures. And this affects a pretty large chunk of the population, about 3%. There’s a sex bias. More women than men get scoliosis. And there’s so many aspects of this disease that we just don’t understand.
Miller: Zebrafish don’t walk obviously and they don’t have to deal with vertical gravity pushing down on their spines the way we do. So what makes them a good animal model?
Bearce: Yeah, I love this question actually because fish spines, at least, may experience life in a more similar fashion than you might think to our own human spine. So fish swim through the water head first. I guess if you want to think about it that way. And those forces that they encounter in that direction are going to be a little bit similar to the way that our spines encounter gravity as we walk upright. So there’s actually more in common with the way that a zebrafish spine bears load than you would think, compared to a walking bipedal person.
Miller: So, do zebrafish have something like scoliosis?
Bearce: Yes. So that’s another thing that has made the fish such a great model organism for this is that zebrafish do develop natural scoliotic-like curves. So spinal curves have been characterized and identified in fish for decades. Actually, for a long time we’ve known that environmental and toxicological agents and pollutants will cause spine curves in fish for reasons that we don’t understand. Aging and bacterial infection are also associated with spinal curves. So it’s really valuable to us that fish naturally develop curves. And that makes them one of the more valuable components of the fish as a model organism. Because it’s something that does arise with some common prevalence in the environment naturally.
Miller: So what did your team want to study exactly?
Bearce: I guess in layman’s terms, my boss, the senior author on this work is Dan Grimes. A few years ago, he characterized a really critical role for the flow of cerebrospinal fluid down the center nervous system as a critical factor that maintains spine straightness in fish. So he characterized a role for motile cilia. These are extracellular structures that mechanically beat to generate fluid flows. And we found that when you disrupt motile cilia and disrupt cerebrospinal fluid flow, as a result of disrupting those, fish during their growth periods in juvenile development, they will actually develop spinal curvature in a way that resembles, very closely, something like an adolescent idiopathic scoliosis.
Miller: What are the potential implications of that finding for humans?
Bearce: In the fish, we’ve characterized that motile cilia provide a lot of the bulk fluid flow of cerebrospinal fluid down the central canal. And this fluid flow talks to cells that it contacts, either with a mechanical signal or possibly a chemical one, by moving these fluids and important components of these fluids down the central canal. And that is really important in a zebrafish spinal canal, because that final canal is incredibly tiny. So we don’t think this works exactly the same way.
We do think fluid flow is incredibly important, potentially in spine straightness in humans as well. But the bulk of fluid flow in the human comes from heartbeat. So we think a lot of the mechanical and chemical sensation pathways that we’re trying to reveal in the fish model are going to be conserved, even if the source of that fluid flow may be different because we are much larger than a fish. So really common parallel processes we believe are underneath both of these processes.
Miller: What are you most excited to study next?
Bearce: I am really excited about what this work overall can tell us about how organs create the right shape in development and then maintain that shape throughout life. It reveals that there’s these active background processes that are always under way that are keeping our bodies in the correct orientations and maintaining the right scales. And I’m fascinated by the basic biology of that. So that is what I’m excited to keep investigating.
Miller: Beth Bearce, thanks for joining us today.
Bearce: Thanks so much.
Miller: Beth Bearce is a cell biologist and a postdoctoral research fellow at the University of Oregon.
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