What is FOXG1?

Until 2008, the rare disease FOXG1 Syndrome was being misdiagnosed as a severe version of something called Rett Syndrome - another neurodevelopmental disorder with similar symptoms. But the truth is that underlying FOXG1 Syndrome are problems with the specific FOXG1 gene - according to UCL researcher Hannah Bruce...

汉娜,在正常情况下,你有两个copies of FOXG1: you get one from your mom and one from your dad, but in a particular disease case called FOXG1 syndrome, you only have one working copy of FOXG1. The FOXG1 gene encodes information to make a protein, which is basically a machine that does a lot of work in your cells.

Phil - And what does that protein then do?

Hannah - The FOXG1 protein is really cool, I think. It's first job is to control the expression of turning on and off of other genes.

Tim - FOXG1 in particular is what we call a transcription factor; that is involved in turning different other genes on and off.

Phil - Like a master control switch or something?

蒂姆-是的h, that's a really good description, yeah. So it controls all these other genes.

Phil - That’s Tim Rittman from the University of Cambridge. I went to see him to try and visualise what the FOXG1 protein actually does - and it’s a vital job for your developing brain that starts in those first few months in the womb.

Phil - Can you help me visualise which parts of the brain this is actually helpful for?

蒂姆-是的h, of course. We've got a model here of the brain...

Phil - And it's a lot bloodier than I normally see a brain!

蒂姆-是的h, so the brain has got this amazing network of blood vessels running all over the top of it. And you're right, this particular model has got all of those blood vessels on.

Phil - I can understand why they don't normally show it, because it's quite disconcerting.

Tim - It's a little bit gory, isn't it?

Phil - Which parts of the brain is FOXG1 going to be most important for?

Tim - So the brain looks a bit like a sort of walnut, really, with all those folds. That cortex is where FOXG1 is really important.

Phil - The top part.

Tim - That's right, yeah. And if we open the brain up, you can just see in the middle here...

Phil - You've given me a cross section here, and it's like the centre of the walnut.

Tim - Just about as far as down in the brain as you can get.

Phil - This set of relatively small lumps is called the basal ganglia.

Tim - So those two things together, these basal ganglia and this cortex, is where FOXG1 is really important.

Phil - Together the cortex and the basal ganglia are called the cerebrum, the top part of your brain. It’s actually the biggest part, and it’s useful for what you might think of as higher human abilities - emotions, complex intelligence, and memories. It includes everything except for some parts near the bottom. And so when you have a problem with FOXG1, all those important areas don’t develop right, and you end up with a visibly smaller brain. The other big issue you face involves a crucial part in the middle of this cerebrum...

Tim - Now of course we've got two hemispheres here, left and right, and there's a really important connection between the two: this C-shaped structure here just below the cortex, just above the basal ganglia. And that is called the corpus callosum.

Phil - It's like a layer between the centre of the walnut and the crinkly, walnut-y part.

Tim - This is the main communication between the left and the right side of the brain. So this is like a massive, huge bunch of telephone wires essentially. And when we see people with FOXG1 problems, that corpus callosum is affected and a lot thinner than it should be. So there's less messages getting from one side of the brain to the other.

Phil - And it’s not like the two hemispheres work fine on their own. These messages are crucial for most of the things the brain does.

Tim - You take something like language, which usually you'd find in the left hemisphere; it's still got to communicate with the right hemisphere, which has some of the same function in it. So this connection between the two is absolutely critical for all of our brain functions, really.