View Full Version : Development riddle

2005-Oct-13, 01:06 AM
This was asked to us by one of the guest lecturers in my neuroscience course. His specialty is development. Take this graph paper (don't worry, I'm hosting this image myself):


This graph paper represents all the cells of an early emrbyo. Imagine the paper is wrapped into a hollow ball. The cells are evenly spaced on the outside of the ball. At this stage every cell is completely identical in every way. The rules are that the cells can only do what normal cells can do. They can communicate amongst each other, but since they are identical here they are all sending the same signals. They can synthesize new chemicals, but which chemicals they synthesize are determined by the DNA, which cannot be changed (no mutation) and the DNA is all producing the same chemicals at this stage. They cannot think or make decisions on their own, everything they can do has to be mediated by chemical changes in the cell. And the chemistry cannot change randomly, everything has to be determined based on cues that follow the rules of chemistry. Additionally, the cells cannot recieve any stimulus from the outside, not even gravity. The only external signals they can detect are from other cells within the grid. Now given that, here is the task:

Make a head.

The point isn't really to make a whole head, but somehow somewhere differences have to develop between the cells. How does this happen? The answer may surprise you.

2005-Oct-13, 09:19 AM
The point isn't really to make a whole head, but somehow somewhere differences have to develop between the cells. How does this happen? The answer may surprise you.

Hmm... if all the cells act at exactly the same time, and are evenly spaced, then the whole thing is degenerate and you can't get any sort of symmetry breaking. I suspect (based on having dated a biology major years ago) that some of the cells kill themselves off, and that creates a difference, which then allows a head to form.

One way to do this is the following:
For each cell that has four neighbours (initally, all of them),
1. create and send out exactly one message to exactly one neighbour (any neighbour).
2. if you receive four messages (three or two messages works, too, but is dangerous because it increases the likelihood of the thing), kill yourself.
3. if you now notice you have fewer than four neighbours, believe that the symmetry is broken and send out development signals.
4. repeat until development signals are received or you have fewer than four neighbours.

That doesn't give a consistent development model (that is, which cells die is somewhat random), but I'd guess it's something like that.

I suppose that since it's a sphere, an axis will necessarily form if you chose a more deterministic method of sending those signals. For instance, any one cell, say the cell at the top of the sphere, could send out a message, which gets stored in the next cell. The next cell passes the message on to another cell that doesn't have the message. This continues until a cell can't pass the message on. That cell kills itself, symmetry is broken (in a consistent way -- only one cell dies), and more complex instructions can occur.

2005-Oct-13, 04:42 PM
Yes, but all cells are exactly the same. They are all sending the exact same messages. They all have the exact same number of neighbors with the exact some proprties. Your method would work, but only after one of the cells becomes different than the others. How could one become different if they are all identical? And how does the emrbyo determine which cells will become different?

The Supreme Canuck
2005-Oct-13, 05:13 PM
You've presented us with a problem. You want all cells to remain the same, but you want them all to form a head that has specialized cells. It is impossible unless you allow some cells that are identical to become different.

It just doesn't work otherwise.

snarkophilus' solution seems to work. All cells start with the same capability to change, and all start with the same ability to initiate this change in others. They all exercise this ability, and some have their capability for change (i.e., death) initiated. So identical cells can become differentiated.

2005-Oct-13, 11:47 PM
Correct, my question is how the cells become different. There must be some chemical mechanism that triggers one cell that is completely identical to all the rest to somehow become different. I am asking what this trigger is. snarkophilus' method describes how they change, but not how that change is ultimately triggered. There must be some ultimate cause that makes one cell out of a bunch of identical cells suddenly decide to do something different. The cells do change, but they have to be told to change by some means.

2005-Oct-14, 12:31 AM
are you leaning towards the magical invisible finger of God intevening and making the cells change?

2005-Oct-14, 01:21 AM
If the cells are indeed absolutely identical, then it results in nothing useful.

When comparing this to the real world of cells, I read it more as: These cells all SEEM to be abolutely identical, and they SEEM to act without influence from any external factors, and I cannot FIND any difference between them, so how does it work?

Because I don't know a difference or an influence doesn't mean there is not one.

There are rules that may not evidence themselves. A cell alone will act one way, even if it has built in rules that say different things to do if it finds itself adjacent to other cells. But once the cells divide a few times and some cells find themselves surrounded by others and some find themselvs on the periphery, these prevously unseen rules will come into play. That is just a rule based upon what the cell bundaries encounter. There are also considerations such as what a cell might do if it has to receive nutrition or other chemical input by way of another cell rather than directly from its environment. That is to say another cell might act as a filter and affect what the cell in question receives. That in turn alters how the cell behaves. For example, if a cell finds itself against another cell on one side, it may cause ions or whatever to migrate either towards or away from that side of the cell. This will leave the far side of the cell with a different makeup chemically, electrically , or whatever. That will affect what can happenn on that free side.

If junior can listen to any music he wants, he might go goofy on us. But if mom hears the music first and only makes office music available to junior, he will not receive that stimulus.

2005-Oct-14, 02:10 AM
The point is that all the cells are identical, and there is all the same structure, so they are all sending and recieving the same message.

I gather I am not making myself very clear. I should probably give the answer.

According to the professor, every cell starts out exactly the same. However, each cell only has a few transcription factors. These factors bind to non-coding segments of DNA, telling the cell to begin reading the following coding segment and thus making the protein or RNA that segment of DNA codes for. This is where the differences arise from. The transcription factors are roaming around mindlessly, like any diffusing substance (i.e. Einstein's "random walk"). Exactly where the few transcription factors in each cell end up is random. Somewhere along the line, one of the transcription factors in one the cells triggers an important gene more quickly than in the other cells. The difference is probably only by a small fraction of a second. But this minute advantage in one cell is all the embryo needs to start developing different structures out of a ball of identical cells. The difference is rapidly amplified, and cell/cell interactions cause others cells to start changing.

We like to think of development as a very specific, carefully orchestrated, highly deterministic series of events that turns us into who we are. The point of this all is that the starting point, the thing that ultimately gives the us our form and structure, is entirely random. There are many other examples in development of these sort of random changes ultimately determining what happens. Often things like what stem cell becomes what adult cell, or where a certain cell ends up going, is entirely random. The processes are carefully orchestrated to give the right proportions of various cells on a large scale, and put the correct cells in the correct places, but on the cellular and several-cell scale things are often quite, or even completely, random. Additionally, the proteins that cause ours neurons to form, our brain to form, are exactly the same chemicals that cause our liver, our kidney, and in fact every structure to form. Every time people find this great signalling protein that is supposed to be the key to a structure developing, it is found in cells throughout an emrbyo. You have bone morphogenic protein triggering neuron growth, for instance. Nothing is unique about the development of our brain compared to our other organs. I just find it interesting. We always think of ourselves as so special, so perfect, to think that what makes us what we are is dependent on completely random occurences is kind of a wake-up-call. To quote my professor, "everything traces back to a first cause, which is stochastic (random)". Moreover, that our wonderful and unique brain is made using the same signalling molecules that make our lungs should also carry a message. There are all these sophisticated events and components involved in development that we always assumed were critical, but we are learning that many of these events and structures are not necessary, an embryo can develop fine without them. To quote Gould, "The most important scientific revolutions all include, as their only common feature, the dethronement of human arrogance from one pedestal after another of previous convictions about our centrality in the cosmos." That's why I thought it was appropriate for this forum, even though it is a biology question and I doubted anyone would have gotten it (nobody in our class got it either, myself including, it even took students in the teacher's own neural development course a while to get it).

2005-Oct-14, 02:57 AM
The difference is probably only by a small fraction of a second.

OK, I had that part, but what happens when a second (or more) cell also has the same thing happen in the small window that exists while the signal, that another cell has volunteered for the duty, travels. Now two cells have "gone first". Which wins? How?

2005-Oct-14, 02:58 AM
I don't know that much about it. We covered the entire neuronal development process in 2 hours. I think once the process starts, the interactions start getting a lot more complicated.

2005-Oct-14, 03:02 AM
I don't know that much about it. We covered the entire neuronal development process in 2 hours. I think once the process starts, the interactions start getting a lot more complicated.
That was the interesting part for me. I know how Ethernet (http://en.wikipedia.org/wiki/Ethernet#CSMA.2FCD_shared_medium_Ethernet) works, how a computer that wants to grab the channel to transmit does it -- while another computer might be about to do the same and only one can use it at the same time. I'm curious if it's the same solution.

2005-Oct-14, 03:19 AM
So, essentially the cells are not truely identical. They're identical in a broad sense in that they're the same type, same age, have the same DNA, etc. But there are small differences of a few molecules/chemicals/transcription factors here and there. And so that's what ends up causing the embyro to differentiate.

It just occurs to me that this is a bit like the birth of the universe... A few quantum flucutuations in a homogenous universe lead to all the structures we see today. A few small molecular imbalances in a homogenous embryo lead to all the different organs in a grown organism. It's interesting how nature parallels itself sometimes.

2005-Oct-14, 05:14 AM
They have the same transcription factors, it is simply that the transcription factors are moving randomly so what part of the DNA they bind to at a given point in time is essentially random.

Ken G
2005-Oct-14, 05:28 AM
This may be the most fascinating thing I've ever heard in biology, and also a great logic puzzle. To me, what it comes down to is, in your rules you said all cells must do the same thing, and be identical. But you never ruled out the possibility that one of the things they could do is, "flip a coin"! In other words, even if all coins are identical, they still come up heads or tails at random. (Diffusion is not quite the same as flipping coins, but in the general sense, this is the key element.) I wonder what IDers would say to this concept-- the embryo is intelligently designed to flip a bunch of coins? It's certainly possible, it is a design that is bound to succeed, but the main thing that IDers are trying to avoid is getting structure out of randomness!

2005-Oct-14, 10:39 PM
Precisley, Ken. That was exactly my reaction as well. You said it much better than I did, thank you. And in fact, the professor even pointed out how religious fundamentalists wouldn't like this because they don't like randomness in biology (my professors all seem to be making these quips about ID).

2005-Oct-15, 03:30 AM
That was the interesting part for me. I know how Ethernet (http://en.wikipedia.org/wiki/Ethernet#CSMA.2FCD_shared_medium_Ethernet) works, how a computer that wants to grab the channel to transmit does it -- while another computer might be about to do the same and only one can use it at the same time. I'm curious if it's the same solution.

So, I'm trying to apply the Ethernet solution to the head-forming scenario and I'm stuck. Ethernet CSMA/CD is basically like a dinner party where one person grabs the floor. Everyone can talk and listen. If it's quiet, and you're inclined, you start. But you listen, too, and if someone else also started talking, you stop, wait for quiet, and try again after a random delay (and the others do likewise). Eventually someone gets the floor and the rest listen (until the speaker runs out of things to say and the process begins again).

OK, cells can send and receive chemical signals. If there's no head-signal present, and a cell is inclined (by chemically randomized chance), it might assert the head-signal and begin doing head things. Another cell that hasn't yet received the inhibiting head-signal might also happen to assert the head-signal soon after. (Non-head cells can amplify the signal, just for propagation's sake, but that doesn't solve anything.) If a head-cell detects head-signal, it stands down, and may try again later, after all head-signaling fades out, after some more random reactions.

The trouble is, how does a head-cell know it's receiving only another cell's head-signal? How can it tell that it's not just receiving its own head-signal? Can it somehow impress on the signal its "ID" so it can tell the difference between a signal from self and a signal from other?

I suppose a solution could just come from a matter of timing. Maybe the "decisions" to be head can only on average happen relatively long times apart, so there is no need for a stand-down and retry process, and the head-signal propagates to the entire body quickly enough that having two head contenders is very, very rare -- and having two heads is better than... no, I mean, maybe having more than one head is non-catastrophic and just, say, yields the occasional (identical) twin or other tuple births.

Well, I'm way out of my element here. Biologist? Embryologist?

Ken G
2005-Oct-15, 03:54 AM
And along similar lines, a sizable fraction of developing embryoes never become viable. This is usually blamed on faulty DNA, but could it sometimes just be bad luck?

2005-Oct-15, 04:25 AM
And along similar lines, a sizable fraction of developing embryoes never become viable. This is usually blamed on faulty DNA, but could it sometimes just be bad luck?Well, to me, that could be the case. Maybe having two head contenders is catastrophic, but that's just the cost of doing business. C'est la vie. Or, c'est la mort. The process doesn't have to be perfect -- just good enough.

Ken G
2005-Oct-15, 04:46 AM
I love how that last statement would imprint itself on ID "theory": "Apparently God isn't perfect, but darn it,
he's good enough for us"!

2005-Oct-15, 09:44 AM
I am not sure I like the word "random" as used here. Not because I think we are special, but because the patterns are there already. It may well be that the starting point is random, but the finished product is not. That first cell is not going to randomly start to become a human in this case, while the next identical cell will randomly start to become a crocodile. The pattern is there already. Not only that, not only will I become a human, I will resemble my dad, have inherited diseases, and so on. It may be random which of the offspring have individual traits of course, but the overall pattern is programmed in.

In this sense. There is a pattern to the numbers around a roulette wheel. Go clockwise around it and the numbers will always come up in the same sequence. You can start any random place on it you like, but once on the track, the sequence is the same.

When I put together a jigsaw puzzle, I pick a piece at random. Well, not quite random, since I pick an edge piece, but that doesn't really narrow it down all that much. But once underway, the pattern to emerge is not random.

By the way, though it turns out to be wrong, my theory of unexposed inner rules allows cells to be identical. Maybe it doesn't allow for as much variation as I like, though, your method does seem better at that. Having a list of "what do I do if?" rules alters the response depending upon environment. They all may send the same signals, but just like a sonar on a submarine, the same signal sent does not always generate the same reply, and the response to that reply is then conditional.

Ken G
2005-Oct-15, 06:39 PM
That's basically what I was wondering, if the DNA pattern is predestined to emerge regardless of the random details, or if in some cases the random details can go badly wrong such that the result encoded by the DNA fails to occur. Identical twins would give some measure of this-- are they ever completely identical, even in the womb? Can one die, and the other live?

2005-Oct-15, 07:19 PM
in a pair of identical twins in the womb, one can die and the other can live.
my brother- the one born 3 years after me- was intitially one of a pair of embryos. but one of them died off a couple months into the pregnancy and was miscarried. my brother was born, but he was always sick and a bit weak. he died of liver cancer at the age of 5. the theory was that they came from the same initial embryo, but one of them was too "sick" to survive to birth, and my brother was born with a genetic defect that essentially gave him cancer from the get-go.
of course, the pregnancy happened in 1976-77 -and my brother died in the fall of '82- so the understanding of what was going on wasn't quite where it would be today.
sometimes, the whole randomness of things just doesn't work out in the long haul.

Ken G
2005-Oct-15, 08:21 PM
I'm very sorry to hear of this tragic event, I didn't realize my question would have such a personal resonance with anyone in the forum. That must have been an awful experience for you and your family, I wish things had gone very differently. Your story does make it sound like there are significant random elements in embryonic development, especially if something has already gone wrong.