Wednesday, October 24, 2007

Knowing your left from right.

The recent couple of posts on left-handedness being superior has rekindled my interest in the origins of left-right symmetry in organisms. A really interesting question is “how does an embryo figure out where top, bottom, front, back, and left and right are?”.
The problem is actually a critical one. Externally, humans are pretty symmetrical. Internally, things are much more complicated. Your left-lung has two lobes, your right has three. Your heart nestles gently in between the middle, but slightly towards the left (which is why the left side is missing a lobe – it’s to fit the heart). Your liver sits to the right, while the other organs are packed around in a non-symmetric way.

There is a group of the population which have this all confused.

Situs invertus is a disorder affecting some 1:8500 people, and which results in (internally) left-being-right and vice versa. Their heart sits to the right, and their right lung has two lobes; their left lung has three. Then there are the unfortunate people who are born with no left-right dissymmetry at all. Swapping left and right seems like an easy thing, when you think about it. Everything would pack normally. If the embryo doesn’t know where to put things, however, then vasculature tends to just connect to whatever is closest – and isomerism results in babies having emergency surgery within hours of birth in order to re-plumb pretty much everything inside.

So how do you figure all this out? Top-bottom and front-back are all formed by the interactions involving Hox genes. Basically, a cluster of cells known as the ‘node’ produces some chemicals which act as transcription factors, and then, as the chemicals get diluted, form a gradient which enables a ‘top’ and a ‘bottom’.

Left and right is much cooler.

It turns out that sitting on the node is a clump of cilia swirling in a counter-clockwise direction.
Nobutaka Hirokawa at the University of Tokyo showed that these cilia produce a leftward flow of fluid over the embryo which is therefore able to give you a left-to-right gradient. The node produces another gradient of factors which flows left to right, giving you a difference in sides. If you culture some mouse embryos, stick a stirrer inside and artificially make the flow go the opposite direction, as Hiroshi Hamada from Osaka University did, you end up with mice suffering from situs invertus.

So, regardless if you're left or right handed... be glad that you can tell left from right.


8 comments:

Anonymous Coward said...

Welcome to the bayblab Doc. Awesome post! We hope there will be many more...

Dominic B. said...

The thing is....for me...left is everything....have a look to my last blog post. Can you name it?

Bayman said...

Great post. Good to have you on board. Interesting how the cilia turn in a left-handed direction. Why left and not right?

The Doc said...

It's probably because all these molecules are stereogenic. Besides, it's irrelevant which way the cilia spin - it's the gradient that is important. Once you have something which distinguishes a left from right side, then you're home-and-hosed.
I just like these sorts of simple solutions that evolution tends to give.

The Doc said...

Dominic,

Firstly, I posit to you that it is no mere coincidence that the latin word for left gives us the root for 'sinister'. Left handedness is evil, and rightly the church has crusaded against all that it stands for.
Left-handers get their own special scissors, because they can't drive the normal ones. Clearly mentally deficient.
Bike helmet straps designed for right-handers, because we're all hoping to weed the lefties out.
Many great rulers were lefties, including the European royals, and the Roman heirarchy... a clear demonstration that left-handedness is a result of inbreeding, and therefore is evil.

Bayman said...

I think we can all agree that if the church thinks left-handedness is evil, it must not be so.

Unless you also accept their laws concerning the origins of the universe and life as well?

So, if it is not so that left-handedness is evil, why has the church gone to such great lengths to perpetuate this myth? Obviously, a conspiracy on the part of the Roman Catholic clergy to marginalize the power of the various left-handed aristocracies, who are indeed the rightful rulers of humanity. We're not talking da Vinci code fables here people, this is a real-life conspiracy.

Bayman said...

the doc said,
"It's probably because all these molecules are stereogenic."

Don't you mean left-handed...???

The Doc said...

No, I mean stereogenic. Stereogenic sounds more smart.

"left handed" just sounds wrong.