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So this is really interesting, not only because fruit flies are interesting, but because fruit
flies are related to all other living organisms, and other animals need to solve the same sort
of problems during development to pattern themselves from head to tail, just as a fruit
fly does.
This is an image, this is a diagram, of a mouse fetus, a mouse developing inside its
mother's womb. Very early on, it also needs to determine the front versus the back, the
top of the head versus the back towards the tail. The same processes that are used in
fruit flies to make head, wings, [and] abdomen are also used in a mouse. Mice don't have
wings - they don't have wings growing out of their backs - but they still have the same
need for specifying the difference between the top part of the back, the middle of the
back where the rib cage comes out, and the tail.
Because mice and fruit flies and all other animals are related, they have the same toolbox,
the same set of tools, for this sort of patterning to happen. Instead of making the wings, they
make some other parts. They use the same domino to start off the cascade; it just goes in
a slightly different direction.
We've seen in flies that a particular mutation in one of these Hox proteins causes an extra
set of wings. Now, if you look to the same mutation in a mouse, we wouldn't expect that
the mouse would grow an extra set of wings. The mouse doesn't even know how to make one
pair of wings. What the mouse does know how to make, under the direction of these particular
control proteins: it knows how to make a ribcage. And some of them say, "Make ribs here." We
would expect, perhaps, that the same sort of mutation that causes double wings in the
fly might have something to do with extra ribs in a mouse, and that's what you see.
So here's a normal mouse. We're looking at it in side view. Here's its backbone, here's
its ribcage. Now, the same sort of mutation, breaking the same kind of proteins in the
same kind of way that causes extra wings in fruit flies, causes a whole bunch of extra
ribs to show up in the mutant mice. You can do another sort of mutation and, instead of
getting too many ribs, you get too few ribs.
So this is telling us that not only are these tools that the fruit fly uses to turn itself
from one ball of goo into something that has an orderly antennae, wings, legs, and so forth...this
same exact toolbox is used in a mouse to turn a mouse from a single egg ball of goo without
a top and a bottom to something that has a head, ribs, and a tail. We've learned all
of this by finding instances where it's broken, and the same kinds of breakages cause similar
effects in very different animals.
And finally, we've seen that similar processes in different animals are used to get the same
outcomes, from top to bottom ordering, but a mouse is much more complicated than a fly.
It also has all sorts of other kinds of order to impose on a ball of goo. In particular,
once you've got the top to bottom figured out, there are still things like the top of
the arm to the bottom of the arm to the tips of the fingers that need to be ordered...and
once a problem is solved in biology by an organism and you have a way of solving that
problem one time in one place, you often find it being reused in other times and other places
to solve similar sorts of problems.
So those same Hox proteins that say, early on, whether this should be the top of the
neck all the way down to the bottom of the tail for a mouse, later on in development
are reused to specify the position along the arm. When certain of those proteins go, you
get a shoulder. WIth others, you get an upper arm, and a lower arm, and then finally fingers.
Again, just as from the front of the fly to the back of the fly, these exact same proteins
are used not to specify where wings ought to go or ribs ought to go, but now where the
forearm ought to go. So when you mess those up, you might expect to see things like extra
forearms, not enough forearms, extra fingers, or not enough fingers. These are starting
to look like real abnormalities that people are affected by. So on the next slide I'm
going to show you an image of a mouse and then a human abnormality, a heartbreaking
developmental abnormality. We understand what causes that abnormality, we understand how
it might be prevented, based on careful study of fruit flies, which seem to have nothing
at all to do with humans.
So this is an example of a human mutation that -- the person doesn't grow extra wings,
but it's the same sort of problem that was understood from studying the fruit flies and
from studying the mice. Here's an example in mice. Here's a normal mouse arm. It's got
a shoulder, an upper arm and a forearm, and this mouse has a shoulder and an upper arm,
and then a hand coming out of where its elbow ought to be.
So, again, the same sort of process that causes a fruit fly to put the wings in the right
place causes in humans fingers to be properly specified, properly made in the right number
and [with] the right connection.
So I've got a couple important lessons, take-home pieces of information to write down in your
notes..
>> TEACHER: [fake coughs]
about what this is actually telling us.
>> Teacher: [fake coughs again] Excuse me!...write this down.
>>Dr. Pincus: So the first lesson is that we're all built
from the same parts. Every animal is built out of the same basic building blocks. People
just have more of them in slightly more complicated patterns. It's the same kind of cells, the
same neurons, put together according to the same rules.
And that's the second major lesson: not only are we built from the same parts, but the
rules, the processes, by which those parts are put together are the same from one organism
to another.
Now you might think, "Why is that?" Well, it's because all organisms are related to
one another by evolution. You might further think, "Well, gosh, a fruit fly is pretty
dissimilar from a mouse...gee, a fruit fly is even pretty dissimilar from a dragonfly.
How related could they really be?" But we saw that it's just one tiny typo in the blueprint
that takes a fruit fly, which looks like a normal fly, to something that all of a sudden
is starting to look a little bit more like a dragonfly. It's got an extra set of wings.
Maybe another tiny typo in its blueprint and the fly gets bigger, it's better able to survive
in some particular kind of place. A few more tiny little typos, we go from something
that looks like a normal fruit fly to something that's looking an awful lot like a dragonfly,
and beyond that it's not that many more steps to get to something that starts to look like
a mouse.
We all come from the same place, all of the pieces are the same, and the tools that we
use to pattern from beginning, from head to tail
or for any biological process are very, very similar across all evolved species. All living
things use the same toolbox in very similar ways and, in fact, reuse these tools not only,
say, from head to toe, but from shoulder to fingertips.
So those are the two main lessons: we're all built out of the same parts, and the processes
are almost identical between very different animals, and that's why we study model organisms.
We exhaustively understand how a tiny fly or a tiny worm work, and that tells us a lot
about how we work.
So if anyone has any questions about fruit flies or worms or the type of work that I
do, I'd be happy to answer them now.
>>TEACHER: But, before we do that, it is customary, when someone has finished a lecture like this,
to give them a sincere and encouraging round of applause.
[applause]