I (Natalie) was at a southern barbecue eating good food and enjoying good company when our book came up in conversation. With it came a request to explain the waves in simple terms. Being surrounded by a bunch of really keen American football fans I invoked the stadium wave.
The stadium wave (also called the Mexican wave) is great fun phenomena where someone starts a “wave” that is made by people in the stands leaping up and putting their arms in air. The wave will travel around the stadium. The differentiation waves are much the same. A sheet of cells is ready to participate in the wave but each cell doesn’t actually stand up and wave its arms until the cell next to it does it first. If you look at the stadium way, the people can watch what other people are doing. A cell has no eyes and no brain. So instead of watching for the wave and watching it as it passes, the cell has its bistable organelle on top to sense if a wave is coming its way. When the cell next to it “waves” it gets its signal to do its thing.
When I was a little girl in Brownies we attended a huge event in honour of Canada’s 100th birthday in 1967. The Montreal Arena was absolutely packed full of little Brownies all in uniform and we each had a cushion. My cushion was yellow on one side and brown on the other. All those in my pack had the same cushion. All the packs sitting in my section had the same colour. Other packs in other sections had other cushions, with different pairs of colours but always light and dark. I recall being absolutely fascinated by how the person directing from the floor was able to make incredible patterns across the stadium by the simple act of saying things like “Everyone on the south side hold up their cushion with the dark side out.” The arena became a brown sea. “Now everyone turn your cushion over!” and suddenly the area erupted in gigantic patches of bright colours.
Imagine a bunch of little girls in their cute little Brownie uniforms but instead of one cushion each Brownie has five cushions. The cushions are numbered 1 through 5. The Brownies are all in their seat and they follow instructions to take out cushion number one and be ready. Cushion number 1 is red on one side and white on the other. Now the leader gives instructions. Everyone on this row, turn your cushions to white. In the row beside them everyone turn their cushions to red. Now “go”. In embryonic terms, the cell is ready with a “cushion” that is the bistable organelle, the cell state splitter. The cell state splitter can either expand or contract in response to an outside mechanical signal or to what the cell next to it can do. Red cushion is analogous to contraction, white to expansion.
The result would be a moving wave of white in one direction and red in the other other that would move around the stadium until the red and white meet on the opposite side and then the wave would stop. We would now have the stadium neatly divided into half red and half white. This is exactly what happens during the embryonic stage in mammals known as compaction. A ball of cells is neatly divided into two parts, the inner cells mass and the outer trophoblast. Instead of red and white we have contraction of the inner cell mass and expansion of the outer trophoblast. The contraction action actually moves the contracted cells into the inside. The expansion results in an outer sphere of cells. The balls of cells of the recently fertilized egg undergoes it first differentiation. The inner cell mass will become the future mammal. The outer sphere will come the placenta, and amniotic sack and other supportive tissue which is later discarded at birth.
What part do “genes” play? Go back to our little Brownies. Now once the first wave has gone by the leader says to the Brownies “Check your cushion for instructions!” The white side of the cushion has printed on it “Put the red and white cushion away and put cushion number 2 (brown and orange) away with it and take out cushion number 3 (green and yellow). The red side of the cushion has the instructions “Put the red and white cushion away and take out cushion number 2 (brown and orange) and put cushion number 3 (green and yellow) aside with the red and white cushion. Now repeat the entire event but this time the two start rows are not at one end of the stadium but instead are started in the middle. Two rows in the middle of the white section are instructed to have one row wave green and the other row wave yellow. Meantime in red section the two rows are to use their brown or orange side respectively. The result of triggering the waves again is the division of the stadium into four sections, brown, orange, green and yellow.
The only “outside” information required to do this division of Brownies in a stadium is to watch the girl next to you and do what she does except for the ones in the start row. This is how the differentiation waves work. The only information a cell has is what the cell next to it does. The response is inherent in the colour of the cushions the child is carrying and the directions on those cushions which is analogous to the genetic code each cell carries. The code includes instructions of which part of the code (cushion) each girl is to use next. The code also contains instructions for which genes (cushions) to put away and not use.
This response to the wave, reading the cushion instructions, is the embryonic process of “determination”. If we wanted to carry the analogy even further, imagine that each little girl has brought a suitcase of clothing along, separated in five numbered bags that match the cushion colors. After she participates in the red wave, the instruction on the cushion include the directive to take out and change into the clothing in one of the bags. Eventually all the girls are wearing a new outfit corresponding to which waves she participated in. This changing of clothing would be analogous to “differentiation” where cells stop producing one set of proteins and change to another set of proteins and in doing so become a new type of cell. The genetic code carries not just the instruction on the cushion (which are signal transduction to the nucleus i.e. determination) but the instructions for how to make the clothing in the suitcases (differentiation). Each different cell uses some of the code but not everything in the code (some cushions nut not others) depending on where the cell is and what sequence of waves it has participated in.
In our cell sheets, the start of the wave is signalled by some mechanical force in the cell sheet instead an announcer/leader. If we take the ectoderm contraction wave as an example, the underlying invagination of mesoderm touching the underside of the sheet of cells is the signal. This mechanical signal is passed from cell to cell the pushing and tugging of neighbours.
The ectoderm contraction wave actually goes through more than one tissue. It starts in tissue that will eventually become notochord then passes through tissue that will become tailbud mesoderm and then finally through to the ectoderm. In early embryogenesis, many of the waves go through more than one tissue. However, if the cell in that tissue has been previously subdivided by earlier waves, the result is simply that the wave passing through more than one tissue type will create a pattern duet each cell having a different set of instructions (or a different cushion). If you look at the “Best Wave” sequence, the audience has previously been divided by being given different cushions. The wave in the stadium simply exposes a preexisting difference in a spectacular fashion. Note how once the wave has created the beer glass pattern, there is another wave inside just the beer glass that empties it visually. A second wave (or third or fourth or fifth) on one section of an embryo but not another allows refinements of the pattern of embryogenesis. In our model, the people who make the beer glass drain would be a tissue type that once triggered is primed to be trigger again even though the people around it stay quiet. Repeat waves are also very common in embryogenesis in development of the early brain, for example.
One other little bit of embryological jargon. A cell can only participate in a wave if it is “competent” as in ready to go. In the case of the beer commercial below, it is like the people waiting, cushions ready, like the people at the beginning to the video.
It is hard to explain the waves of embryogenesis in few sentences in a break between barbecued steak and key lime pie to a group of people whose sole common interest, aside from being related, is that we have all watch football. But the stadium wave, and my experience as a Brown back in 1967, served as an excellent analogy where everyone seemed to “get it”. Yes, “the genes” do it but waves explain why genes only “do it” in the right place at the right time.