Which way is up?

Let’s engage in a little thought experiment for a minute.

Imagine that you are a cell on the inner surface of your intestine. Your job is to transfer food (or rather, the nutrients resulting from food’s digestion) from the interior of the intestine to the bloodstream. It’s really important, therefore, that you know which side of you faces the intestine and which side faces the bloodstream. But how do you know which side is which?

Now imagine that you are a plant; specifically, you are a part of the plant that is about to bud into a leaf. It’s really important, therefore, that you develop as a leaf, and not as a flower or a root or an extension of the stem. But how do you know that which end of you is the part that connects back to the stem, and which part is supposed to flatten out into the leaf tip?

Finally, imagine that you are a developing fly. (Gross, perhaps, but bear with me.) As you go from embryo to larva, your body must pattern itself in such a way that you wind up with a head at one end, wings in the middle, and a tail at the other. It’s really important your body gets oriented correctly, or else you won’t hatch. But how do you know which end is supposed to be the head?

If you look at the world from a human perspective, it’s easy to know how to orient yourself for any task – can I walk on my feet, could I sit on a chair, or do I have to stand on my head? From the perspective of a cell, however, the task of orienting yourself is a little trickier. But it’s extremely important. If a cell gets its orientation wrong, the consequences could be dire – nutrients won’t get sent into the bloodstream, neurons will not send the right messages to the right places, entire pieces of anatomy could develop incorrectly, even entire organisms could die. This question of how cells orient themselves properly is quite a large topic. Every single cell in the world has “directionality” – top and bottom, left and right, front and back. How they do this is vast and complicated, and I’m not going to go into all of the ways it is done today. I just want to highlight a specific example: how does a developing fly know which end is the head and which is the tail?

A fly’s life begins with the fertilization of an egg. This single cell will then divide over and over to produce thousands of cells needed to make the final fly. And this single cell already contains the information to determine which end is the head and which end is the tail. The information is crucial from the very start of the fly’s life, because the early cells that are produced build on that information to reinforce the body plan. This all happens through the use of protein gradients.

Take a look at the diagram below. I’ve drawn an example of the protein gradients that help determine a fly’s head and tail. The single egg contains a gradient of proteins, which are called maternal-effect proteins. In this picture, there are 2 such proteins – blue and pink. There is a lot of blue at what will be the head, and a lot of pink at what will be the tail. In the middle, there is a mixture of both. Cell that are surrounded by a lot of blue protein know that they are in the head, cells surrounded by a lot of pink protein know that they are in the tail, and cells with some of both know that they are somewhere in the middle. These maternal-effect proteins cause each cell to produce different proteins themselves, based on where they are. First come the gap proteins, which subdivide the body plan. The gap proteins then specify production of the pair-rule proteins, which make segments along the body. Finally, the pair-rule proteins specify which segment polarity proteins get made, which tell each segment which end points to the head and which to the tail. The combined action of all of these proteins tell each cell where it is in relation to the overall body. And that information helps each cell develop properly – so that the fly gets wings on his back, legs from his belly and eyes on his head.

This model of using protein gradients to specify orientation is commonly used in developing multicellular organisms, including mammals. Of course, as the animal gets more complex (with limbs, organs, and highly developed brains), the system of patterning gets more complex, too. It’s a topic that is being intensely studied among developmental biologists to this day. And it will probably continue to be studied for many years to come.