Neural crest cells: crawling around the embryo

These cells contribute to almost all your organs, how do they get in position?
23 November 2020

Interview with 

Paul Kulesa, Stowers Institute for Medical Research


Drawing of human embryo


Every single one of us exists because a sperm successfully fertilised an egg. But the resulting embryo faces a problem: how to ensure that the trillions of cells that it gives rise to - and which make up the body - end up in the right places. One group of cells is called the neural crest. They form down the length of the embryo above what’s going to become the spinal cord. But from there, they have to migrate around to the front of the embryo - passing through lots of other developing tissues on the way - to give rise to a host of different structures including the nerves supplying the skin, melanocytes that give us our protection from the sun, and they even form the face. These feats of navigation mean the neural crest can teach us a huge amount about how cells move, and Paul Kulesa, from the Stowers Institute for medical research, studies how they do it, and what can sometimes go wrong, as he told Eva Higginbotham...

Paul - Neural crest cells are a multipotent cell type. That means they can become a number of different types of cells that include neurons and bone and cartilage and pigment cells. And they contribute to nearly every organ. But the problem is that neural crest cells must travel long distances to reach peripheral targets, where they contribute to organ assembly. They encounter complex developing tissues during migration in an embryo that's growing and undergoing tremendous amounts of dynamic movements of the underlying tissues through which they're crawling in the fibers. So it's a very dynamic microenvironment and it's as if they're crawling through a very dense like Amazon jungle, but the jungle is dynamic and moving and growing plants as they're trying to get through the jungle.

Eva - So these cells are sort of crawling through this complicated surface of other cells and other things that are going on. How do they actually move themselves forward?

Paul - Well, we know from cell culture studies that cells will extend a protrusion and then anchor that protrusion and then degrade whatever fibers are in their way and attach to something that they can hold on to, and then pick up the attachments behind at the backend of the cell and then pull themselves forward.

Eva - Is that kind of like how you kind of think of a slug moving or a snail, they kind of push out some part of themselves and then drag themselves along?

Paul - Right, right. Very much so because you can see in vivo, when you're imaging, you can see bits and pieces of the cell membrane that are left behind actually, as the cells are crawling through. And so it's almost going back to the analogy of the jungle as if they're going through very dense thorny bushes and shrubs and getting pieces of clothing ripped off on the thorny bushes as you go. And it's very much so it seems like with the cells.

Eva - How do they manage to actually force a protrusion out? Cause if they're moving through this really dense forest, how do they get enough sort of energy and force behind them to push a protrusion between cells to allow them to sort of dig their way through?

Paul - Right. Well, there's a couple of different ways that we know of that cells can do this. They can start to initiate a protrusion of the membrane by bringing in machinery of the cell, which builds fibers in the cell. But there's also another way that a cell can initiate a protrusion and that's by opening water channels, aquaporins, within the cell membrane. So Aqua for water and pour for porins. And having water do the job to initiate the protrusion.

Eva - Like creating holes almost that allow the bit of the membrane that they want to force its way through, to kind of inflate?

Paul - Right. It's as if in the dense jungle, there's only small gaps, then you can stick your arm through there and then cut away at the fibers in order for you to then move more of your body through that dense jungle.

Eva - What happens if something goes wrong in that process?

Paul - Ah, well, if they can't make it to their target in the head, then the cranial facial pattern can be disrupted because they give rise to bone and cartilage of the face. And so two of the more common human birth defects are cleft lip or cleft palate, or problems with the nerves that innervate your jaw. And neural crest cells contribute to the heart. And so you can have congenital birth defects to the heart flow tracks. One of the major early pediatric cancers is neuroblastoma. It is a solid tumor that forms outside of the brain. And it's very common in infants that are zero to five years old. And what happens is the neural crest cells that are contributing to the peripheral nervous system and becoming neurons and having to wire a neural circuit have some malfunction and that can lead to pediatric neuroblastoma. We're looking to see whether aquaporins and other invasion genes that are typical of the embryonic neural crest relate at all to predicting the potential of a neuroblastoma as a solid tumor to become what's called metastatic or to leave the primary tumor site and invade other tissues.

Eva - So are these aquaporins prevalent in other cancers that we know are likely to metastasize?

Paul - Yes, well, there's been some work in glioblastoma recently. That's compared patient samples of the tumor core versus infiltrating cells. And we know that aquaporin-1 is expressed by the infiltrating cells. So certainly in glioblastoma and in other invasive cancers. So it may be that it's both predictive of metastatic potential and a clinical target.


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