If you recall how baby is formed, you start as a single cell and, eventually, it divides into several trillion cells. I want you to take a moment and imagine that family tree. There's some serious great-grandma cells on that family tree.
In the tiny worm C. elegans, scientists patiently mapped every single cell division from egg to adult, and named every one of the 1031 cells that arise. And they did it decades ago with nothing more than a microscope.
Never complaining about how many cousins you have ever again, right?
In the mouse it is not so easy. Challenge number one: the mouse is not a transparent organism. Challenge number two: the mouse has rather more than 1031 cells. Challenge number three: the mouse does all of these cell divisions inside of another mouse. Dammit, mammals.
Knowing more about the which cells are the grandparent cells in a given tissue is a pretty important question. In particular, grandma cells tend to be stem cells, and stem cells are a BFD (Big Fucking Deal). So say you have a certain type of cell and you looked at it and you said, wow, yeah, I think that these guys are grandma cells, and that all these cells over here are grandbaby cells. How would you know for sure?
Step one: pick a protein that only the grandma cells are making, a marker protein, if you will. Now what you really want is the on switch that tells the cell to make that particular protein. You're going to do a nifty swap in the next step, and you want the cell to turn on your swapped out protein as if it was your marker protein.
Step two: Cre! Cre is a protein that chews up DNA, but only DNA that is flanked by two very specific sequences. It is a heat-seeking DNA missile -- it is a the sort of protein that makes its presence known in a controlled and persistent way. The Cre gets hooked to the on switch of your marker protein.
Now you have a DNA attack dog that you can unleash only in your grandma cells. You just need to give it some DNA to attack.
Step three: the DNA that's going to get attacked is a roadblock. Here's what you put into the mouse, as a DNA sequence: first, a MAKE LOTS OF THIS signal, followed by a STOP NEVERMIND DON'T DO THAT signal, and finally the instructions for how to make GLOWY SHIT (fluorescent protein, to split hairs). The STOP signal is flanked by the sequences I mentioned earlier that tell Cre to chew it all to shit. If the Cre is unleashed on this sequence, it goes to town on the STOP signal, and the message edited message is to MAKE LOTS of GLOWY SHIT. The cell will light up like a pinball machine with a high score.
Since the Cre changed the DNA, and DNA doesn't fuck around changing the rules once they've been laid down, all the daughter cells and grandbaby cells will also light up. Because only the grandma cells have the Cre, only cells descended directly from those particular cells will glow.
Step four: check that shit out under a microscope and see if you were right! It should be obvious.
Step five: bask in your scientific discovery! Hooray! You did it, you did the biology thing. Gold star.
