WHEN I found out I was pregnant the first time, the embryo that was to become my son was already busy doing the same as the zebrafish embryo whose development I was filming on the microscope that day. Both were undergoing neurulation, one of the first major shape changes in their lives: a flat sheet of cells was folding into the neural tube that would become their spinal cord and brain.
There are good reasons to be interested in neurulation. Neural tube defects are very common, affecting about 1 in 1000 newborns. Every year, more than 100 babies in Britain are born with conditions such as spina bifida, where the neural tube in the spinal region does not close completely and the sufferer loses control of legs, bowels and bladder. In addition, around 700 pregnancies end in abortion or stillbirth due to neural tube defects.
We know that neural tube defects can be caused by a myriad of events, from genetic mutations to excessive alcohol exposure. There is even a pretty good way to prevent them: taking folic acid from before conception until the end of the third month of pregnancy reduces the incidence of neural tube defects by around 50 per cent. However, we still barely understand how folic acid achieves this, probably because we know surprisingly little about what actually happens during neurulation.
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This is where my research starts. I watch zebrafish neurulate. The zebrafish embryo grows from a single cell into a tiny fish, complete with brain and beating heart, in only 24 hours. It is also transparent, which is great if you want to watch what鈥檚 going on inside. I label the outlines of all the cells in my zebrafish with a green fluorescent protein and then film the embryo during neurulation.
By doing this, I can follow the cells as the zebrafish develops. I watch them grow, change shape, divide and bend. I observe how they send out tentacles, squeeze between their neighbours and move around on complex paths. Think of people at sports events doing Mexican waves and you get the idea 鈥� except that the fish display is much more bizarre and beautiful. What exactly is it about the dance of the cells that causes a fish to fold? How do you get from a flat sheet to a tube? And what happens in embryos where neurulation goes wrong 鈥� how do the cells behave differently?
鈥淭he display is like a bizarre and beautiful Mexican wave鈥�
As with most research, some of my daily work can be painfully dull. Once I have made a good movie, I need to draw around each and every cell of interest to reconstruct its shape 鈥� often by hand. I thereby create a digital copy of the piece of embryo that I am studying, and this we then analyse quantitatively, using customised software tailor-made by other lab members.
The result is a precise description of how the behaviours of individual cells make the neural tube. My reconstructed cells are like pieces in a complex three-dimensional jigsaw that changes shape every few minutes. By comparing mutant zebrafish with normal ones, I have also discovered that a normal-looking neural tube can form even if it lacks specific medial cells with specialised shapes, but we yet have to discover exactly how the cells that take their place achieve this.
We still have a long way to go from here to understanding and preventing more neural tube defects. I recently found out that I am pregnant again. With another folding project going on this close to my heart, I worry about spina bifida like any other mum-to-be. But I have taken my folic acid and now all I can do is sit back and hope that the choreography of my baby鈥檚 neural cells is just as robust as that of their zebrafish counterparts on my microscope.
